bekhterevОбозрение психиатрии и медицинской психологии имени В.М.БехтереваV.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY2313-70532713-055XV. M. BEKHTEREV NATIONAL RESEARCH MEDICAL CENTER FOR PSYCHIATRY AND NEUROLOGY OF THE RUSSIAN FEDERATION MINISTRY OF HEALTH10.31363/2313-7053-2022-56-3-13-29bekhterev-716Research ArticleНАУЧНЫЕ ОБЗОРЫSCIENTIFIC REVIEWРоль дофамина и норадреналина в алкоголь-зависимом поведении: от корреляций к механизмамDopamine and norepinephrine role in alcohol-addictive behavior: from correlations to mechanismshttps://orcid.org/0000-0003-3744-8231ГриневичВ. П.GrinevichV. P.

Гриневич Владимир Павлович – к.б.н./PhD, адьюнкт-профессор, ведущий специалист направления «Нейробиолигия» НЦ генетики и наук о жизни

Краснодарский край

Vladimir P. Grinevich

Krasnodarsky Region

grinevich.vp@talantiuspeh.ruhttps://orcid.org/0000-0002-1222-6926НемецВ. В.NemetsV. V.

Немец Всеволод Владимирович – аспирант и младший научный сотрудник Института трансляционной биомедицины

Санкт-Петербург

Vsevolod V. Nemets

St. Petersburg

v.v.nemets@spbu.ruhttps://orcid.org/0000-0002-0529-4525КрупицкийЕ. М.KrupitskyE. M.

Крупицкий Евгений Михайлович – д.м.н., профессор, заместитель директора по научной работе и руководитель отдела аддиктологии; руководитель лаборатории клинической фармакологии аддиктивных состояний в институте фармакологии им. А.В.Вальдмана

Санкт-Петербург

Evgeny M. Krupitsky

St. Petersburg

kruenator@gmail.comhttps://orcid.org/0000-0003-2951-6038ГайнетдиновР. Р.GainetdinovR. R.

Гайнетдинов Рауль Радикович – к.м.н., директор Института трансляционной биомедицины и научный руководитель Клиники высоких медицинских технологий им. Н. И. Пирогова; руководитель группы направления «Нейроболигия» НЦ генетики и наук о жизни

Краснодарский край;

Санкт-Петербург

 

Raul R. Gainetdinov

Krasnodarsky Region;

St. Petersburg

gainetdinov.raul@gmail.comhttps://orcid.org/0000-0002-5675-0279БудыгинЕ. А.BudyginE. A.

Будыгин Евгений Александрович — к.б.н., профессор, руководитель Направления «Нейробиология» НЦ генетики и наук о жизни

Краснодарский край

Evgeny A. Budygin

Krasnodarsky Region

budygin.ea@talantiuspeh.ruНаучно-технологический университет «Сириус», ФТ СириусРоссияSirius University of Science and Technology, FD SiriusRussian FederationСанкт-Петербургский государственный университетРоссияSt. Petersburg State UniversityRussian FederationНациональный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева; Первый Санкт-Петербургский государственный медицинский университет им. И.П. ПавловаРоссияV.M. Bekhterev National Medical Research Center for Psychiatry and Neurology; St.-Petersburg First Pavlov State Medical UniversityRussian FederationНаучно-технологический университет «Сириус», ФТ Сириус; Санкт-Петербургский государственный университетРоссияSirius University of Science and Technology, FD Sirius; St. Petersburg State UniversityRussian Federation2022151020225631329Copyright © Гриневич В.П., Немец В.В., Крупицкий Е.М., Гайнетдинов Р.Р., Будыгин Е.А., 20222022Гриневич В.П., Немец В.В., Крупицкий Е.М., Гайнетдинов Р.Р., Будыгин Е.А.Grinevich V.P., Nemets V.V., Krupitsky E.M., Gainetdinov R.R., Budygin E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.bekhterevreview.com/jour/article/view/716

Используя модели на животных, воспроизводящие ключевые характеристики алкогольной зависимости, был достигнут значительный прогресс в идентификации нейрохимических субстратов данного заболевания, ведущую роль среди которых играют дофамин и норадреналин. Последние внедрения оптогенетических технологий в область алкогольных исследований предоставили возможность идентифицировать в пределах дофаминергической и норадренергической систем специфические паттерны нейропередачи, которые формируют этанол-зависимое поведение. Представляемый обзор литературы преимущественно сфокусирован на экспериментальных исследованиях, демонстрирующих эффективность современных технологий в раскрытии катехоламиновых механизмов аддиктивного поведения, направленного на употребление алкоголя.

Using animal models that translate key features of alcohol dependence, the field has faced remarkable achievements in identifying neurochemical substrates of this disease with dopamine and norepinephrine playing significant role. Moreover, recent utilization of optogenetics in alcohol research provides with an opportunity in specifying patterns of neurotransmission within dopaminergic and noradrenergic neural circuits that govern ethanol-addictive behavior. This review summarizes experimental findings to demonstrate the effectiveness of the latest technologies in revealing the mechanisms bridging catecholamines’ specific changes with alcohol seeking, consummatory and relapsing behaviors.

этанолалкогольная зависимостьповедениедофаминнорадреналинвольтамметрияоптогенетикаethanolalcohol dependencebehaviordopaminenorepinephrinevoltammetryoptogeneticsв рамках проекта за номером NRB-RND-2114 «Нейрохимические механизмы патологических мотиваций при нервно-психических расстройствах и их фармакологическая коррекция». Немец В.В. был поддержан в рамках проекта за номером 93018770 Санкт-Петербургского государственного университета. Авторы статьи выражают благодарность Герасимовой Елене Вячеславовне за помощь в оформлении литературы.the work was supported by the Sirius University of Science and Technology within the framework of the project number NRB-RND-2114 «Neurochemical mechanisms of pathological motivations in neuropsychiatric disorders and their pharmacological correction». Vsevolod V. Nemets was supported under project number 93018770 of St. Petersburg State University. The authors of the article express their gratitude to Elena V. Gerasimova for her help in preparing the literature.ReferencesПанченко Л.Ф., Брюсов О.С., Балашов А.М., Гриневич В.П., Островский Ю.М. Взаимодействие некоторых алкалоидов тетрагидроизохинолина с опиатными рецепторами в гипоталамусе и среднем мозге крыс. Вопр. Мед. Хим. 1982;28(5):88-92.Panchenko LF, Brusov OS, Balashov AM, Grinevich VP, Ostrovsky YM Interactions of some tetrahydroisoquinoline alkaloids with opiate receptors in the rat hypothalamus and midbrain. Vopr Med Khim. 1982;28(5):88-92. (In Russ).Паценко А.А., Гриневич В.П. Высокая эффективность тетрагидроизохинолинов по отношению к сайтам связывания с высоким сродством дофамина в полосатом теле крысы. Нейрохимия. 1988;79(1):33-38.Patsenko AA, Grinevich VP. High potency of tetrahydroisoquinolines to dopamine high affinity binding sites in rat striatum. Neurokhimiya. 1988;79(1):33-38. (In Russ).Паценко А.А., Гриневич В.П. Определение содержание сальсолинола в полосатом теле крысы радиометрическим методом. ВИНИТИ. 1987;27250-В87:1-14.Patsenko AA, Grinevich VP, Olshevskaya AB Radiochemical micromethod for the determination of the catehol-O-methyltransferase activity in rat tissues. VINITI.1987;2830-B87:1-9. (In Russ).Паценко А.А., Гриневич В.П., Островский Ю.М. Взаимодействие простых тетрагидроизохинолинов с опиатными и высокоаффинными дофаминовыми (D3) рецепторами в полосатом теле крысы. Фармакол. Токсикол. 1987;4:33-35.Patsenko AA, Grinevich VP, Ostrovsky YuM. Interaction of simple tetrahydroisoquinolines with opiate and high-affinity dopamine (D3) receptors in the rat corpus striatum. Farmakol. Toksikol. 1987; 50:33-35. (In Russ).Adamantidis AR, Tsai HC, Boutrel B, Zhang F, Stuber GD, Budygin EA, Touriño C, Bonci A, Deisseroth K, de Lecea L. Optogenetic interrogation of dopaminergic modulation of the multiple phases of reward-seeking behavior. J Neurosci. 2011;31(30):10829-10835. https://doi.org/10.1523/jneurosci.2246-11.2011Adamantidis AR, Tsai HC, Boutrel B, Zhang F, Stuber GD, Budygin EA, Touriño C, Bonci A, Deisseroth K, de Lecea L. Optogenetic interrogation of dopaminergic modulation of the multiple phases of reward-seeking behavior. J Neurosci. 2011;31(30):10829-10835. https://doi.org/10.1523/jneurosci.2246-11.2011Anstrom KK, Miczek KA, Budygin E. Increased phasic dopamine signaling in the mesolimbic pathway during social defeat in rats. Neuroscience. 2009;161(1):3-12.Anstrom KK, Miczek KA, Budygin E. Increased phasic dopamine signaling in the mesolimbic pathway during social defeat in rats. Neuroscience. 2009;161(1):3-12.Aston-Jones G, Bloom FE. Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci. 1981;1(8):876-886. https://doi.org/10.1523/jneurosci.01-08-00876.1981Aston-Jones G, Bloom FE. Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci. 1981;1(8):876-886. https://doi.org/10.1523/jneurosci.01-08-00876.1981Aston-Jones G, Cohen JD. An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci. 2005;28:403-450. https://doi.org/10.1146/annurev.neu-ro.28.061604.135709Aston-Jones G, Cohen JD. An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci. 2005;28:403-450. https://doi.org/10.1146/annurev.neu-ro.28.061604.135709Bailey CP, O’Callaghan MJ, Croft AP, Manley SJ, Little HJ. Alterations in mesolimbic dopamine function during the abstinence period following chronic ethanol consumption. Neuropharmacology. 2001;41(8):989-999. https://doi.org/10.1016/s0028-3908(01)00146-0Bailey CP, O’Callaghan MJ, Croft AP, Manley SJ, Little HJ. Alterations in mesolimbic dopamine function during the abstinence period following chronic ethanol consumption. Neuropharmacology. 2001;41(8):989-999. https://doi.org/10.1016/s0028-3908(01)00146-0Barak S, Carnicella S, Yowell QV, Ron D. Glial cell line-derived neurotrophic factor reverses alcoholinduced allostasis of the mesolimbic dopaminergic system: implications for alcohol reward and seeking. J Neurosci. 2011;31(27):9885-9894. https://doi.org/10.1523/jneurosci.1750-11.2011Barak S, Carnicella S, Yowell QV, Ron D. Glial cell line-derived neurotrophic factor reverses alcoholinduced allostasis of the mesolimbic dopaminergic system: implications for alcohol reward and seeking. J Neurosci. 2011;31(27):9885-9894. https://doi.org/10.1523/jneurosci.1750-11.2011Bass CE, Grinevich VP, Gioia D, Day-Brown J, Bonin KD, Stuber GD, Weiner JL, Budygin E. Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration. Frontiers in behavioral neuroscience. 2013;7:173.Bass CE, Grinevich VP, Gioia D, Day-Brown J, Bonin KD, Stuber GD, Weiner JL, Budygin E. Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration. Frontiers in behavioral neuroscience. 2013;7:173.Bassareo V, Frau R, Maccioni R, Caboni P, Manis C, Peana AT, Migheli R, Porru S, Acquas E. Ethanol-Dependent Synthesis of Salsolinol in the Posterior Ventral Tegmental Area as Key Mechanism of Ethanol’s Action on Mesolimbic Dopamine. Front Neurosci. 2021;15:675061. https://doi.org/10.3389/fnins.2021.675061Bassareo V, Frau R, Maccioni R, Caboni P, Manis C, Peana AT, Migheli R, Porru S, Acquas E. Ethanol-Dependent Synthesis of Salsolinol in the Posterior Ventral Tegmental Area as Key Mechanism of Ethanol’s Action on Mesolimbic Dopamine. Front Neurosci. 2021;15:675061. https://doi.org/10.3389/fnins.2021.675061Berry MD, Gainetdinov RR, Hoener MC, Shahid M. Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges. Pharmacology & therapeutics. 2017;180:161-180.Berry MD, Gainetdinov RR, Hoener MC, Shahid M. Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges. Pharmacology & therapeutics. 2017;180:161-180.Boileau I, Assaad JM, Pihl RO, Benkelfat C, Leyton M, Diksic M, Tremblay RE, Dagher A. Alcohol promotes dopamine release in the human nucleus accumbens. Synapse. 2003;49(4):226-231. https://doi.org/10.1002/syn.10226Boileau I, Assaad JM, Pihl RO, Benkelfat C, Leyton M, Diksic M, Tremblay RE, Dagher A. Alcohol promotes dopamine release in the human nucleus accumbens. Synapse. 2003;49(4):226-231. https://doi.org/10.1002/syn.10226Borg S, Kvande H, Sedvall G. Central norepinephrine metabolism during alcohol intoxication in addicts and healthy volunteers. Science. 1981;213(4512):1135-1137. https://doi.org/10.1126/science.7268421Borg S, Kvande H, Sedvall G. Central norepinephrine metabolism during alcohol intoxication in addicts and healthy volunteers. Science. 1981;213(4512):1135-1137. https://doi.org/10.1126/science.7268421Borodovitsyna O, Joshi N, Chandler D. Persistent Stress-Induced Neuroplastic Changes in the Locus Coeruleus/Norepinephrine System. Neural Plast. 2018;2018:1892570. https://doi.org/10.1155/2018/1892570Borodovitsyna O, Joshi N, Chandler D. Persistent Stress-Induced Neuroplastic Changes in the Locus Coeruleus/Norepinephrine System. Neural Plast. 2018;2018:1892570. https://doi.org/10.1155/2018/1892570Bradaia A, Trube G, Stalder H, Norcross RD, Ozmen L, Wettstein JG, Pinard A, Buchy D, Gassmann M, Hoener MC, Bettler B. The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proc Natl Acad Sci USA. 2009;106(47):20081-20086. https://doi.org/10.1073/pnas.0906522106Bradaia A, Trube G, Stalder H, Norcross RD, Ozmen L, Wettstein JG, Pinard A, Buchy D, Gassmann M, Hoener MC, Bettler B. The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proc Natl Acad Sci USA. 2009;106(47):20081-20086. https://doi.org/10.1073/pnas.0906522106Brodie MS. Increased ethanol excitation of dopaminergic neurons of the ventral tegmental area after chronic ethanol treatment. Alcohol Clin Exp Res. 2002;26(7):1024-1030. https://doi.org/10.1097/01.alc.0000021336.33310.6bBrodie MS. Increased ethanol excitation of dopaminergic neurons of the ventral tegmental area after chronic ethanol treatment. Alcohol Clin Exp Res. 2002;26(7):1024-1030. https://doi.org/10.1097/01.alc.0000021336.33310.6bBudygin EA. Dopamine uptake inhibition is positively correlated with cocaine-induced stereotyped behavior. Neurosci Lett. 2007;429(1):55-8. 10.1016/j.neulet.2007.09.064Budygin EA. Dopamine uptake inhibition is positively correlated with cocaine-induced stereotyped behavior. Neurosci Lett. 2007;429(1):55-8. 10.1016/j.neulet.2007.09.064Budygin EA, Bass CE, Grinevich VP, Deal AL, Bonin KD, Weiner JL. Opposite consequences of tonic and phasic increases in accumbal dopamine on alcohol-seeking behavior. IScience. 2020;23(3):100877.Budygin EA, Bass CE, Grinevich VP, Deal AL, Bonin KD, Weiner JL. Opposite consequences of tonic and phasic increases in accumbal dopamine on alcohol-seeking behavior. IScience. 2020;23(3):100877.Budygin EA, John CE, Mateo Y, Daunais JB, Friedman DP, Grant KA, Jones SR. Chronic ethanol exposure alters presynaptic dopamine function in the striatum of monkeys: a preliminary study. Synapse. 2003;50(3):266-268.Budygin EA, John CE, Mateo Y, Daunais JB, Friedman DP, Grant KA, Jones SR. Chronic ethanol exposure alters presynaptic dopamine function in the striatum of monkeys: a preliminary study. Synapse. 2003;50(3):266-268.Budygin EA, John CE, Mateo Y, Daunais JB, Friedman DP, Grant KA, Jones SR. Chronic ethanol exposure alters presynaptic dopamine function in the striatum of monkeys: a preliminary study. Synapse. 2003;50(3):266-268. https://doi.org/10.1002/syn.10269Budygin EA, John CE, Mateo Y, Daunais JB, Friedman DP, Grant KA, Jones SR. Chronic ethanol exposure alters presynaptic dopamine function in the striatum of monkeys: a preliminary study. Synapse. 2003;50(3):266-268. https://doi.org/10.1002/syn.10269Budygin EA, Oleson EB, Mathews TA, Läck AK, Diaz MR, McCool BA, Jones SR. Effects of chronic alcohol exposure on dopamine uptake in rat nucleus accumbens and caudate putamen. Psychopharmacology (Berl). 2007;193(4):495-501. https://doi.org/10.1007/s00213-007-0812-1Budygin EA, Oleson EB, Mathews TA, Läck AK, Diaz MR, McCool BA, Jones SR. Effects of chronic alcohol exposure on dopamine uptake in rat nucleus accumbens and caudate putamen. Psychopharmacology (Berl). 2007;193(4):495-501. https://doi.org/10.1007/s00213-007-0812-1Budygin EA, Phillips PE, Robinson DL, Kennedy AP, Gainetdinov RR, Wightman RM. Effect of acute ethanol on striatal dopamine neurotransmission in ambulatory rats. J Pharmacol Exp Ther. 2001;297(1):27-34.Budygin EA, Phillips PE, Robinson DL, Kennedy AP, Gainetdinov RR, Wightman RM. Effect of acute ethanol on striatal dopamine neurotransmission in ambulatory rats. J Pharmacol Exp Ther. 2001;297(1):27-34.Budygin EA, Phillips PE, Wightman RM, Jones SR. Terminal effects of ethanol on dopamine dynamics in rat nucleus accumbens: an in vitro voltammetric study. Synapse. 2001;42(2):77-79. https://doi.org/10.1002/syn.1101Budygin EA, Phillips PE, Wightman RM, Jones SR. Terminal effects of ethanol on dopamine dynamics in rat nucleus accumbens: an in vitro voltammetric study. Synapse. 2001;42(2):77-79. https://doi.org/10.1002/syn.1101Charlet K, Beck A, Heinz A. The dopamine system in mediating alcohol effects in humans. Curr Top Behav Neurosci. 2013;13:461-488. https://doi.org/10.1007/7854_2011_130Charlet K, Beck A, Heinz A. The dopamine system in mediating alcohol effects in humans. Curr Top Behav Neurosci. 2013;13:461-488. https://doi.org/10.1007/7854_2011_130Chen X, Zheng X, Ali S, Guo M, Zhong R, Chen Z, Zhang Y, Qing H, Deng Y. Isolation and Sequencing of Salsolinol Synthase, an Enzyme Catalyzing Salsolinol Biosynthesis. ACS Chem Neurosci. 2018;9(6):1388-1398. https://doi.org/10.1021/acschemneuro.8b00023Chen X, Zheng X, Ali S, Guo M, Zhong R, Chen Z, Zhang Y, Qing H, Deng Y. Isolation and Sequencing of Salsolinol Synthase, an Enzyme Catalyzing Salsolinol Biosynthesis. ACS Chem Neurosci. 2018;9(6):1388-1398. https://doi.org/10.1021/acschemneuro.8b00023Clayton EC, Rajkowski J, Cohen JD, Aston-Jones G. Phasic activation of monkey locus ceruleus neurons by simple decisions in a forced-choice task. J Neurosci. 2004;24(44):9914-9920. https://doi.org/10.1523/jneurosci.2446-04.2004Clayton EC, Rajkowski J, Cohen JD, Aston-Jones G. Phasic activation of monkey locus ceruleus neurons by simple decisions in a forced-choice task. J Neurosci. 2004;24(44):9914-9920. https://doi.org/10.1523/jneurosci.2446-04.2004Corrodi H, Fuxe K, Hökfelt T. The effect of ethanol on the activity of central catecholamine neurones in rat brain. J Pharm Pharmacol. 1966;18(12):821-823. https://doi.org/10.1111/j.2042-7158.1966.tb07817.xCorrodi H, Fuxe K, Hökfelt T. The effect of ethanol on the activity of central catecholamine neurones in rat brain. J Pharm Pharmacol. 1966;18(12):821-823. https://doi.org/10.1111/j.2042-7158.1966.tb07817.xCurtis AL, Leiser SC, Snyder K, Valentino RJ. Predator stress engages corticotropin-releasing factor and opioid systems to alter the operating mode of locus coeruleus norepinephrine neurons. Neuropharmacology. 2012;62(4):1737-1745. https://doi.org/10.1016/j.neuropharm.2011.11.020Curtis AL, Leiser SC, Snyder K, Valentino RJ. Predator stress engages corticotropin-releasing factor and opioid systems to alter the operating mode of locus coeruleus norepinephrine neurons. Neuropharmacology. 2012;62(4):1737-1745. https://doi.org/10.1016/j.neuropharm.2011.11.020Cushman P, Jr., Forbes R, Lerner W, Stewart M. Alcohol withdrawal syndromes: clinical management with lofexidine. Alcohol Clin Exp Res. 1985;9(2):103-108. https://doi.org/10.1111/j.1530-0277.1985.tb05527.xCushman P, Jr., Forbes R, Lerner W, Stewart M. Alcohol withdrawal syndromes: clinical management with lofexidine. Alcohol Clin Exp Res. 1985;9(2):103-108. https://doi.org/10.1111/j.1530-0277.1985.tb05527.xDarrouj J, Puri N, Prince E, Lomonaco A, Spevetz A, Gerber DR. Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal. Ann Pharmacother. 2008;42(11):1703-1705. https://doi.org/10.1345/aph.1K678Darrouj J, Puri N, Prince E, Lomonaco A, Spevetz A, Gerber DR. Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal. Ann Pharmacother. 2008;42(11):1703-1705. https://doi.org/10.1345/aph.1K678Deal AL, Bass CE, Grinevich VP, Delbono O, Bonin KD, Weiner JL, Budygin EA. Bidirectional Control of Alcohol-drinking Behaviors Through Locus Coeruleus Optoactivation. Neuroscience. 2020;443:84-92. https://doi.org/10.1016/j.neuroscience.2020.07.024Deal AL, Bass CE, Grinevich VP, Delbono O, Bonin KD, Weiner JL, Budygin EA. Bidirectional Control of Alcohol-drinking Behaviors Through Locus Coeruleus Optoactivation. Neuroscience. 2020;443:84-92. https://doi.org/10.1016/j.neuroscience.2020.07.024Deal AL, Konstantopoulos JK, Weiner JL, Budygin EA. Exploring the consequences of social defeat stress and intermittent ethanol drinking on dopamine dynamics in the rat nucleus accumbens. Scientific reports. 2018;8(1):1-9.Deal AL, Konstantopoulos JK, Weiner JL, Budygin EA. Exploring the consequences of social defeat stress and intermittent ethanol drinking on dopamine dynamics in the rat nucleus accumbens. Scientific reports. 2018;8(1):1-9.Deehan GA, Jr., Brodie MS, Rodd ZA. What is in that drink: the biological actions of ethanol, acetaldehyde, and salsolinol. Curr Top Behav Neurosci. 2013;13:163-184. https://doi.org/10.1007/7854_2011_198Deehan GA, Jr., Brodie MS, Rodd ZA. What is in that drink: the biological actions of ethanol, acetaldehyde, and salsolinol. Curr Top Behav Neurosci. 2013;13:163-184. https://doi.org/10.1007/7854_2011_198Diana M. The dopamine hypothesis of drug addiction and its potential therapeutic value. Front Psychiatry. 2011;2:64. https://doi.org/10.3389/fpsyt.2011.00064Diana M. The dopamine hypothesis of drug addiction and its potential therapeutic value. Front Psychiatry. 2011;2:64. https://doi.org/10.3389/fpsyt.2011.00064Diana M, Peana AT, Sirca D, Lintas A, Melis M, Enrico P. Crucial role of acetaldehyde in alcohol activation of the mesolimbic dopamine system. Ann N Y Acad Sci. 2008;1139:307-317. https://doi.org/10.1196/annals.1432.009Diana M, Peana AT, Sirca D, Lintas A, Melis M, Enrico P. Crucial role of acetaldehyde in alcohol activation of the mesolimbic dopamine system. Ann N Y Acad Sci. 2008;1139:307-317. https://doi.org/10.1196/annals.1432.009Diana M, Pistis M, Carboni S, Gessa GL, Rossetti ZL. Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: electrophysiological and biochemical evidence. Proc Natl Acad Sci USA. 1993;90(17):7966-7969. https://doi.org/10.1073/pnas.90.17.7966Diana M, Pistis M, Carboni S, Gessa GL, Rossetti ZL. Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: electrophysiological and biochemical evidence. Proc Natl Acad Sci USA. 1993;90(17):7966-7969. https://doi.org/10.1073/pnas.90.17.7966Diana M, Pistis M, Muntoni A, Gessa G. Mesolimbic dopaminergic reduction outlasts ethanol withdrawal syndrome: evidence of protracted abstinence. Neuroscience. 1996;71(2):411-415. https://doi.org/10.1016/0306-4522(95)00482-3Diana M, Pistis M, Muntoni A, Gessa G. Mesolimbic dopaminergic reduction outlasts ethanol withdrawal syndrome: evidence of protracted abstinence. Neuroscience. 1996;71(2):411-415. https://doi.org/10.1016/0306-4522(95)00482-3Diana M, Rossetti ZL, Gessa G. Rewarding and aversive effects of ethanol: interplay of GABA, glutamate and dopamine. Alcohol Alcohol Suppl. 1993;2:315-319.Diana M, Rossetti ZL, Gessa G. Rewarding and aversive effects of ethanol: interplay of GABA, glutamate and dopamine. Alcohol Alcohol Suppl. 1993;2:315-319.Ding ZM, Rodd ZA, Engleman EA, McBride WJ. Sensitization of ventral tegmental area dopamine neurons to the stimulating effects of ethanol. Alcohol Clin Exp Res. 2009;33(9):1571-1581. https://doi.org/10.1111/j.1530-0277.2009.00985.xDing ZM, Rodd ZA, Engleman EA, McBride WJ. Sensitization of ventral tegmental area dopamine neurons to the stimulating effects of ethanol. Alcohol Clin Exp Res. 2009;33(9):1571-1581. https://doi.org/10.1111/j.1530-0277.2009.00985.xDoyon WM, York JL, Diaz LM, Samson HH, Czachowski CL, Gonzales RA. Dopamine activity in the nucleus accumbens during consummatory phases of oral ethanol self-administration. Alcohol Clin Exp Res. 2003;27(10):1573-1582. https://doi.org/10.1097/01.alc.0000089959.66222.b8Doyon WM, York JL, Diaz LM, Samson HH, Czachowski CL, Gonzales RA. Dopamine activity in the nucleus accumbens during consummatory phases of oral ethanol self-administration. Alcohol Clin Exp Res. 2003;27(10):1573-1582. https://doi.org/10.1097/01.alc.0000089959.66222.b8Duncan CC, Fernando PW. Effects of tetrahydropapaveroline in the nucleus accumbens and the ventral tegmental area on ethanol preference in the rat. Alcohol. 1991;8(2):87-90. https://doi.org/10.1016/0741-8329(91)91314-rDuncan CC, Fernando PW. Effects of tetrahydropapaveroline in the nucleus accumbens and the ventral tegmental area on ethanol preference in the rat. Alcohol. 1991;8(2):87-90. https://doi.org/10.1016/0741-8329(91)91314-rEdwards S, Guerrero M, Ghoneim OM, Roberts E, Koob GF. Evidence that vasopressin V1b receptors mediate the transition to excessive drinking in ethanol-dependent rats. Addict Biol. 2012;17(1):76-85. https://doi.org/10.1111/j.1369-1600.2010.00291.xEdwards S, Guerrero M, Ghoneim OM, Roberts E, Koob GF. Evidence that vasopressin V1b receptors mediate the transition to excessive drinking in ethanol-dependent rats. Addict Biol. 2012;17(1):76-85. https://doi.org/10.1111/j.1369-1600.2010.00291.xFeltmann K, Fredriksson I, Wirf M, Schilström B, Steensland P. The monoamine stabilizer (-)- OSU6162 counteracts downregulated dopamine output in the nucleus accumbens of long-term drinking Wistar rats. Addict Biol. 2016;21(2):438-449. https://doi.org/10.1111/adb.12304Feltmann K, Fredriksson I, Wirf M, Schilström B, Steensland P. The monoamine stabilizer (-)- OSU6162 counteracts downregulated dopamine output in the nucleus accumbens of long-term drinking Wistar rats. Addict Biol. 2016;21(2):438-449. https://doi.org/10.1111/adb.12304Fitzgerald PJ. Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine. Subst Abuse. 2013;7:171-183. https://doi.org/10.4137/sart.s13019Fitzgerald PJ. Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine. Subst Abuse. 2013;7:171-183. https://doi.org/10.4137/sart.s13019Foddai M, Dosia G, Spiga S, Diana M. Acetaldehyde increases dopaminergic neuronal activity in the VTA. Neuropsychopharmacology. 2004;29(3):530-536. https://doi.org/10.1038/sj.npp.1300326Foddai M, Dosia G, Spiga S, Diana M. Acetaldehyde increases dopaminergic neuronal activity in the VTA. Neuropsychopharmacology. 2004;29(3):530-536. https://doi.org/10.1038/sj.npp.1300326Fox HC, Anderson GM, Tuit K, Hansen J, Kimmerling A, Siedlarz KM, Morgan PT, Sinha R. Prazosin effects on stress- and cue-induced craving and stress response in alcohol-dependent individuals: preliminary findings. Alcohol Clin Exp Res. 2012;36(2):351-360. https://doi.org/10.1111/j.1530-0277.2011.01628.xFox HC, Anderson GM, Tuit K, Hansen J, Kimmerling A, Siedlarz KM, Morgan PT, Sinha R. Prazosin effects on stress- and cue-induced craving and stress response in alcohol-dependent individuals: preliminary findings. Alcohol Clin Exp Res. 2012;36(2):351-360. https://doi.org/10.1111/j.1530-0277.2011.01628.xFreeman AS, Meltzer LT, Bunney BS. Firing properties of substantia nigra dopaminergic neurons in freely moving rats. Life Sci. 1985;36(20):1983-1994. 10.1016/0024-3205(85)90448-5Freeman AS, Meltzer LT, Bunney BS. Firing properties of substantia nigra dopaminergic neurons in freely moving rats. Life Sci. 1985;36(20):1983-1994. 10.1016/0024-3205(85)90448-5Gilpin NW, Koob GF. Effects of β-adrenoceptor antagonists on alcohol drinking by alcohol-dependent rats. Psychopharmacology (Berl). 2010;212(3):431-439. https://doi.org/10.1007/s00213-010-1967-8Gilpin NW, Koob GF. Effects of β-adrenoceptor antagonists on alcohol drinking by alcohol-dependent rats. Psychopharmacology (Berl). 2010;212(3):431-439. https://doi.org/10.1007/s00213-010-1967-8Gilpin NW, Weiner JL. Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder. Genes Brain Behav. 2017;16(1):15-43. https://doi.org/10.1111/gbb.12349Gilpin NW, Weiner JL. Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder. Genes Brain Behav. 2017;16(1):15-43. https://doi.org/10.1111/gbb.12349Gonzales RA, Job MO, Doyon WM. The role of mesolimbic dopamine in the development and maintenance of ethanol reinforcement. Pharmacol Ther. 2004;103(2):121-146. https://doi.org/10.1016/j.pharmthera.2004.06.002Gonzales RA, Job MO, Doyon WM. The role of mesolimbic dopamine in the development and maintenance of ethanol reinforcement. Pharmacol Ther. 2004;103(2):121-146. https://doi.org/10.1016/j.pharmthera.2004.06.002Grace AA. Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience. 1991;41(1):1-24. https://doi.org/10.1016/0306-4522(91)90196-uGrace AA. Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience. 1991;41(1):1-24. https://doi.org/10.1016/0306-4522(91)90196-uGrace AA. The tonic/phasic model of dopamine system regulation and its implications for understanding alcohol and psychostimulant craving. Addiction. 2000;95 Suppl 2:S119-128. https://doi.org/10.1080/09652140050111690Grace AA. The tonic/phasic model of dopamine system regulation and its implications for understanding alcohol and psychostimulant craving. Addiction. 2000;95 Suppl 2:S119-128. https://doi.org/10.1080/09652140050111690Grace AA, Bunney BS. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons--1. Identification and characterization. Neuroscience. 1983;10(2):301-315. https://doi.org/10.1016/0306-4522(83)90135-5Grace AA, Bunney BS. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons--1. Identification and characterization. Neuroscience. 1983;10(2):301-315. https://doi.org/10.1016/0306-4522(83)90135-5Grace AA, Bunney BS. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons--2. Action potential generating mechanisms and morphological correlates. Neuroscience. 1983;10(2):317-331. https://doi.org/10.1016/0306-4522(83)90136-7Grace AA, Bunney BS. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons--2. Action potential generating mechanisms and morphological correlates. Neuroscience. 1983;10(2):317-331. https://doi.org/10.1016/0306-4522(83)90136-7Grace AA, Bunney BS. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons--3. Evidence for electrotonic coupling. Neuroscience. 1983;10(2):333-348. https://doi.org/10.1016/0306-4522(83)90137-9Grace AA, Bunney BS. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons--3. Evidence for electrotonic coupling. Neuroscience. 1983;10(2):333-348. https://doi.org/10.1016/0306-4522(83)90137-9Grace AA, Bunney BS. The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci. 1984;4(11):2877-2890. https://doi.org/10.1523/jneurosci.04-11-02877.1984Grace AA, Bunney BS. The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci. 1984;4(11):2877-2890. https://doi.org/10.1523/jneurosci.04-11-02877.1984Grace AA, Bunney BS. The control of firing pattern in nigral dopamine neurons: single spike firing. J Neurosci. 1984;4(11):2866-2876. https://doi.org/10.1523/jneurosci.04-11-02866.1984Grace AA, Bunney BS. The control of firing pattern in nigral dopamine neurons: single spike firing. J Neurosci. 1984;4(11):2866-2876. https://doi.org/10.1523/jneurosci.04-11-02866.1984Grant KA. The role of 5-HT3 receptors in drug dependence. Drug Alcohol Depend. 1995;38(2):155-71. https://doi.org/10.1016/0376-8716(95)01120-nGrant KA. The role of 5-HT3 receptors in drug dependence. Drug Alcohol Depend. 1995;38(2):155-71. https://doi.org/10.1016/0376-8716(95)01120-nGrant S. Let’s not be impulsive: comments on Lubman et al. 2004.Grant S. Let’s not be impulsive: comments on Lubman et al. 2004.Haass-Koffler CL, Swift RM, Leggio L. Noradrenergic targets for the treatment of alcohol use disorder. Psychopharmacology (Berl). 2018;235(6):1625-1634. https://doi.org/10.1007/s00213-018-4843-6Haass-Koffler CL, Swift RM, Leggio L. Noradrenergic targets for the treatment of alcohol use disorder. Psychopharmacology (Berl). 2018;235(6):1625-1634. https://doi.org/10.1007/s00213-018-4843-6Hawley RJ, Major LF, Schulman EA, Lake CR. CSF levels of norepinephrine during alcohol withdrawal. Arch Neurol. 1981;38(5):289-292. https://doi.org/10.1001/arch-neur.1981.00510050055008Hawley RJ, Major LF, Schulman EA, Lake CR. CSF levels of norepinephrine during alcohol withdrawal. Arch Neurol. 1981;38(5):289-292. https://doi.org/10.1001/arch-neur.1981.00510050055008Heilig M, Egli M, Crabbe JC, Becker HC. Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked? Addict Biol. 2010;15(2):169-184. https://doi.org/10.1111/j.1369-1600.2009.00194.xHeilig M, Egli M, Crabbe JC, Becker HC. Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked? Addict Biol. 2010;15(2):169-184. https://doi.org/10.1111/j.1369-1600.2009.00194.xHietala J, West C, Syvälahti E, Någren K, Lehikoinen P, Sonninen P, Ruotsalainen U. Striatal D2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence. Psychopharmacology (Berl). 1994;116(3):285-290. https://doi.org/10.1007/bf02245330Hietala J, West C, Syvälahti E, Någren K, Lehikoinen P, Sonninen P, Ruotsalainen U. Striatal D2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence. Psychopharmacology (Berl). 1994;116(3):285-290. https://doi.org/10.1007/bf02245330Hipólito L, Sánchez MJ, Polache A, Granero L. Brain metabolism of ethanol and alcoholism: an update. Curr Drug Metab. 2007;8(7):716-727. https://doi.org/10.2174/138920007782109797Hipólito L, Sánchez MJ, Polache A, Granero L. Brain metabolism of ethanol and alcoholism: an update. Curr Drug Metab. 2007;8(7):716-727. https://doi.org/10.2174/138920007782109797Hunt WA, Majchrowicz E. Alterations in the turnover of brain norepinephrine and dopamine in alcohol-dependent rats. J Neurochem. 1974;23(3):549-552. https://doi.org/10.1111/j.1471-4159.1974.tb06058.xHunt WA, Majchrowicz E. Alterations in the turnover of brain norepinephrine and dopamine in alcohol-dependent rats. J Neurochem. 1974;23(3):549-552. https://doi.org/10.1111/j.1471-4159.1974.tb06058.xHyland BI, Reynolds JN, Hay J, Perk CG, Miller R. Firing modes of midbrain dopamine cells in the freely moving rat. Neuroscience. 2002;114(2):475-492. https://doi.org/10.1016/s0306-4522(02)00267-1Hyland BI, Reynolds JN, Hay J, Perk CG, Miller R. Firing modes of midbrain dopamine cells in the freely moving rat. Neuroscience. 2002;114(2):475-492. https://doi.org/10.1016/s0306-4522(02)00267-1Imperato A, Di Chiara G. Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther. 1986;239(1):219-228.Imperato A, Di Chiara G. Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther. 1986;239(1):219-228.Jadzic D, Bassareo V, Carta AR, Carboni E. Nicotine, cocaine, amphetamine, morphine, and ethanol increase norepinephrine output in the bed nucleus of stria terminalis of freely moving rats. Addict Biol. 2021;26(1):e12864. https://doi.org/10.1111/adb.12864Jadzic D, Bassareo V, Carta AR, Carboni E. Nicotine, cocaine, amphetamine, morphine, and ethanol increase norepinephrine output in the bed nucleus of stria terminalis of freely moving rats. Addict Biol. 2021;26(1):e12864. https://doi.org/10.1111/adb.12864Jones SR, Mathews TA, Budygin EA. Effect of moderate ethanol dose on dopamine uptake in rat nucleus accumbens in vivo. Synapse. 2006;60(3):251-255. https://doi.org/10.1002/syn.20294Jones SR, Mathews TA, Budygin EA. Effect of moderate ethanol dose on dopamine uptake in rat nucleus accumbens in vivo. Synapse. 2006;60(3):251-255. https://doi.org/10.1002/syn.20294Juarez B, Morel C, Ku SM, Liu Y, Zhang H, Montgomery S, Gregoire H, Ribeiro E, Crumiller M, Roman- Ortiz C, Walsh JJ, Jackson K, Croote DE, Zhu Y, Zhang S, Vendruscolo LF, Edwards S, Roberts A, Hodes GE, Lu Y, Calipari ES, Chaudhury D, Friedman AK, Han MH. Midbrain circuit regulation of individual alcohol drinking behaviors in mice. Nat Commun. 2017;8(1):2220. https://doi.org/10.1038/s41467-017-02365-8Juarez B, Morel C, Ku SM, Liu Y, Zhang H, Montgomery S, Gregoire H, Ribeiro E, Crumiller M, Roman- Ortiz C, Walsh JJ, Jackson K, Croote DE, Zhu Y, Zhang S, Vendruscolo LF, Edwards S, Roberts A, Hodes GE, Lu Y, Calipari ES, Chaudhury D, Friedman AK, Han MH. Midbrain circuit regulation of individual alcohol drinking behaviors in mice. Nat Commun. 2017;8(1):2220. https://doi.org/10.1038/s41467-017-02365-8Karkhanis AN, Alexander NJ, McCool BA, Weiner JL, Jones SR. Chronic social isolation during adolescence augments catecholamine response to acute ethanol in the basolateral amygdala. Synapse. 2015;69(8):385-395.Karkhanis AN, Alexander NJ, McCool BA, Weiner JL, Jones SR. Chronic social isolation during adolescence augments catecholamine response to acute ethanol in the basolateral amygdala. Synapse. 2015;69(8):385-395.Karkhanis AN, Locke JL, McCool BA, Weiner JL, Jones SR. Social isolation rearing increases nucleus accumbens dopamine and norepinephrine responses to acute ethanol in adulthood. Alcohol Clin Exp Res. 2014;38(11):2770-2779. https://doi.org/10.1111/acer.12555Karkhanis AN, Locke JL, McCool BA, Weiner JL, Jones SR. Social isolation rearing increases nucleus accumbens dopamine and norepinephrine responses to acute ethanol in adulthood. Alcohol Clin Exp Res. 2014;38(11):2770-2779. https://doi.org/10.1111/acer.12555Kenna GA, Haass-Koffler CL, Zywiak WH, Edwards SM, Brickley MB, Swift RM, Leggio L. Role of the α1 blocker doxazosin in alcoholism: a proofof-concept randomized controlled trial. Addict Biol. 2016;21(4):904-914. https://doi.org/10.1111/adb.12275Kenna GA, Haass-Koffler CL, Zywiak WH, Edwards SM, Brickley MB, Swift RM, Leggio L. Role of the α1 blocker doxazosin in alcoholism: a proofof-concept randomized controlled trial. Addict Biol. 2016;21(4):904-914. https://doi.org/10.1111/adb.12275Kessler RC, Crum RM, Warner LA, Nelson CB, Schulenberg J, Anthony JC. Lifetime co-occurrence ofDSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey. Arch Gen Psychiatry. 1997;54(4):313-321. https://doi.org/10.1001/arch-psyc.1997.01830160031005Kessler RC, Crum RM, Warner LA, Nelson CB, Schulenberg J, Anthony JC. Lifetime co-occurrence ofDSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey. Arch Gen Psychiatry. 1997;54(4):313-321. https://doi.org/10.1001/arch-psyc.1997.01830160031005Khemiri L, Steensland P, Guterstam J, Beck O, Carlsson A, Franck J, Jayaram-Lindström N. The effects of the monoamine stabilizer (-)-OSU6162 on craving in alcohol dependent individuals: A human laboratory study. Eur Neuropsychopharmacol. 2015;25(12):2240-2251. https://doi.org/10.1016/j.euroneuro.2015.09.018Khemiri L, Steensland P, Guterstam J, Beck O, Carlsson A, Franck J, Jayaram-Lindström N. The effects of the monoamine stabilizer (-)-OSU6162 on craving in alcohol dependent individuals: A human laboratory study. Eur Neuropsychopharmacol. 2015;25(12):2240-2251. https://doi.org/10.1016/j.euroneuro.2015.09.018Koob GF. Alcoholism: allostasis and beyond. Alcohol Clin Exp Res. 2003;27(2):232-243. https://doi.org/10.1097/01.alc.0000057122.36127.c2Koob GF. Alcoholism: allostasis and beyond. Alcohol Clin Exp Res. 2003;27(2):232-243. https://doi.org/10.1097/01.alc.0000057122.36127.c2Koob GF. Allostatic view of motivation: implications for psychopathology. Nebr Symp Motiv. 2004;50:1-18.Koob GF. Allostatic view of motivation: implications for psychopathology. Nebr Symp Motiv. 2004;50:1-18.Kranzler HR, Soyka M. Diagnosis and Pharmacotherapy of Alcohol Use Disorder: A Review. Jama. 2018;320(8):815-824. https://doi.org/10.1001/jama.2018.11406Kranzler HR, Soyka M. Diagnosis and Pharmacotherapy of Alcohol Use Disorder: A Review. Jama. 2018;320(8):815-824. https://doi.org/10.1001/jama.2018.11406Leo D, Mus L, Espinoza S, Hoener M, Sotnikova T, Gainetdinov R. Taar1-mediated modulation of presynaptic dopaminergic neurotransmission: role of D2 dopamine autoreceptors. Neuropharmacology. 2014;81:283-291.Leo D, Mus L, Espinoza S, Hoener M, Sotnikova T, Gainetdinov R. Taar1-mediated modulation of presynaptic dopaminergic neurotransmission: role of D2 dopamine autoreceptors. Neuropharmacology. 2014;81:283-291.Liu Y, Jean-Richard-Dit-Bressel P, Yau JO, Willing A, Prasad AA, Power JM, Killcross S, Clifford CWG, McNally GP. The Mesolimbic Dopamine Activity Signatures of Relapse to Alcohol-Seeking. J Neurosci. 2020;40(33):6409-6427. https://doi.org/10.1523/jneurosci.0724-20.2020Liu Y, Jean-Richard-Dit-Bressel P, Yau JO, Willing A, Prasad AA, Power JM, Killcross S, Clifford CWG, McNally GP. The Mesolimbic Dopamine Activity Signatures of Relapse to Alcohol-Seeking. J Neurosci. 2020;40(33):6409-6427. https://doi.org/10.1523/jneurosci.0724-20.2020Lynch LJ, Sullivan KA, Vallender EJ, Rowlett JK, Platt DM, Miller GM. Trace amine associated receptor 1 modulates behavioral effects of ethanol. Subst Abuse. 2013;7:117-126. https://doi.org/10.4137/sart.s12110Lynch LJ, Sullivan KA, Vallender EJ, Rowlett JK, Platt DM, Miller GM. Trace amine associated receptor 1 modulates behavioral effects of ethanol. Subst Abuse. 2013;7:117-126. https://doi.org/10.4137/sart.s12110Matsubara K, Fukushima S, Fukui Y. A systematic regional study of brain salsolinol levels during and immediately following chronic ethanol ingestion in rats. Brain Res. 1987;413(2):336-43. https://doi.org/10.1016/0006-8993(87)91025-0Matsubara K, Fukushima S, Fukui Y. A systematic regional study of brain salsolinol levels during and immediately following chronic ethanol ingestion in rats. Brain Res. 1987;413(2):336-43. https://doi.org/10.1016/0006-8993(87)91025-0McCall JG, Al-Hasani R, Siuda ER, Hong DY, Norris AJ, Ford CP, Bruchas MR. CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety. Neuron. 2015;87(3):605-620. https://doi.org/10.1016/j.neuron.2015.07.002McCall JG, Al-Hasani R, Siuda ER, Hong DY, Norris AJ, Ford CP, Bruchas MR. CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety. Neuron. 2015;87(3):605-620. https://doi.org/10.1016/j.neuron.2015.07.002McCall JG, Siuda ER, Bhatti DL, Lawson LA, McElligott ZA, Stuber GD, Bruchas MR. Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior. Elife. 2017;6. https://doi.org/10.7554/eLife.18247McCall JG, Siuda ER, Bhatti DL, Lawson LA, McElligott ZA, Stuber GD, Bruchas MR. Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior. Elife. 2017;6. https://doi.org/10.7554/eLife.18247McCool BA, Chappell AM. Early social isolation in male Long-Evans rats alters both appetitive and consummatory behaviors expressed during operant ethanol self-administration. Alcohol Clin Exp Res. 2009;33(2):273-282. https://doi.org/10.1111/j.1530-0277.2008.00830.xMcCool BA, Chappell AM. Early social isolation in male Long-Evans rats alters both appetitive and consummatory behaviors expressed during operant ethanol self-administration. Alcohol Clin Exp Res. 2009;33(2):273-282. https://doi.org/10.1111/j.1530-0277.2008.00830.xMcCoy JG, Strawbridge C, McMurtrey KD, Kane VB, Ward CP. A re-evaluation of the role of tetrahydropapaveroline in ethanol consumption in rats. Brain Res Bull. 2003;60(1-2):59-65. https://doi.org/10.1016/s0361-9230(03)00018-2McCoy JG, Strawbridge C, McMurtrey KD, Kane VB, Ward CP. A re-evaluation of the role of tetrahydropapaveroline in ethanol consumption in rats. Brain Res Bull. 2003;60(1-2):59-65. https://doi.org/10.1016/s0361-9230(03)00018-2Mejias-Aponte CA. Specificity and impact of adrenergic projections to the midbrain dopamine system. Brain Res. 2016;1641(Pt B):258-273. https://doi.org/10.1016/j.brainres.2016.01.036Mejias-Aponte CA. Specificity and impact of adrenergic projections to the midbrain dopamine system. Brain Res. 2016;1641(Pt B):258-273. https://doi.org/10.1016/j.brainres.2016.01.036Melchior CL, Myers RD. Preference for alcohol evoked by tetrahydropapaveroline (THP) chronically infused in the cerebral ventricle of the rat. Pharmacol Biochem Behav. 1977;7(1):19-35. 10.1016/0091-3057(77)90006-5Melchior CL, Myers RD. Preference for alcohol evoked by tetrahydropapaveroline (THP) chronically infused in the cerebral ventricle of the rat. Pharmacol Biochem Behav. 1977;7(1):19-35. 10.1016/0091-3057(77)90006-5Melis M, Diana M, Enrico P, Marinelli M, Brodie MS. Ethanol and acetaldehyde action on central dopamine systems: mechanisms, modulation, and relationship to stress. Alcohol. 2009;43(7):531-539. https://doi.org/10.1016/j.alcohol.2009.05.004Melis M, Diana M, Enrico P, Marinelli M, Brodie MS. Ethanol and acetaldehyde action on central dopamine systems: mechanisms, modulation, and relationship to stress. Alcohol. 2009;43(7):531-539. https://doi.org/10.1016/j.alcohol.2009.05.004Melis M, Spiga S, Diana M. The dopamine hypothesis of drug addiction: hypodopaminergic state. Int Rev Neurobiol. 2005;63:101-154. https://doi.org/10.1016/s0074-7742(05)63005-xMelis M, Spiga S, Diana M. The dopamine hypothesis of drug addiction: hypodopaminergic state. Int Rev Neurobiol. 2005;63:101-154. https://doi.org/10.1016/s0074-7742(05)63005-xMikhailova MA, Bass CE, Grinevich VP, Chappell AM, Deal AL, Bonin KD, Weiner JL, Gainetdinov RR, Budygin EA. Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors. Neuroscience. 2016;333:54-64.Mikhailova MA, Bass CE, Grinevich VP, Chappell AM, Deal AL, Bonin KD, Weiner JL, Gainetdinov RR, Budygin EA. Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors. Neuroscience. 2016;333:54-64.Moorman DE, Aston-Jones G. Neuroscience: Optical control of reward. Nature. 2009;458(7241):980-1. https://doi.org/10.1038/458980aMoorman DE, Aston-Jones G. Neuroscience: Optical control of reward. Nature. 2009;458(7241):980-1. https://doi.org/10.1038/458980aMorikawa H, Morrisett RA. Ethanol action on dopaminergic neurons in the ventral tegmental area: interaction with intrinsic ion channels and neurotransmitter inputs. Int Rev Neurobiol. 2010;91:235-288. https://doi.org/10.1016/s0074-7742(10)91008-8Morikawa H, Morrisett RA. Ethanol action on dopaminergic neurons in the ventral tegmental area: interaction with intrinsic ion channels and neurotransmitter inputs. Int Rev Neurobiol. 2010;91:235-288. https://doi.org/10.1016/s0074-7742(10)91008-8Mravec B. Salsolinol, a derivate of dopamine, is a possible modulator of catecholaminergic transmission: a review of recent developments. Physiol Res. 2006;55(4):353-364.Mravec B. Salsolinol, a derivate of dopamine, is a possible modulator of catecholaminergic transmission: a review of recent developments. Physiol Res. 2006;55(4):353-364.Myers RD. Tetrahydroisoquinolines and alcoholism: where are we today? Alcohol Clin Exp Res. 1996;20(3):498-500. https://doi.org/10.1111/j.1530-0277.1996.tb01081.xMyers RD. Tetrahydroisoquinolines and alcoholism: where are we today? Alcohol Clin Exp Res. 1996;20(3):498-500. https://doi.org/10.1111/j.1530-0277.1996.tb01081.xMyers RD, Oblinger MM. Alcohol drinking in the rat induced by acute intra-cerebral infusion of two tetrahydroisoquinolines and a beta-carboline. Drug Alcohol Depend. 1977;2(5-6):469-483. https://doi.org/10.1016/0376-8716(77)90047-3Myers RD, Oblinger MM. Alcohol drinking in the rat induced by acute intra-cerebral infusion of two tetrahydroisoquinolines and a beta-carboline. Drug Alcohol Depend. 1977;2(5-6):469-483. https://doi.org/10.1016/0376-8716(77)90047-3Nakahara D, Maruyama W, Hashiguti H, Naoi M. Characterization of the in vivo action of (R)- salsolinol, an endogenous metabolite of alcohol, on serotonin and dopamine metabolism: a microdialysis study. Brain Res. 1994;644(2):226-232. https://doi.org/10.1016/0006-8993(94)91684-5Nakahara D, Maruyama W, Hashiguti H, Naoi M. Characterization of the in vivo action of (R)- salsolinol, an endogenous metabolite of alcohol, on serotonin and dopamine metabolism: a microdialysis study. Brain Res. 1994;644(2):226-232. https://doi.org/10.1016/0006-8993(94)91684-5Nam HW, Bruner RC, Choi DS. Adenosine signaling in striatal circuits and alcohol use disorders. Mol Cells. 2013;36(3):195-202. https://doi.org/10.1007/s10059-013-0192-9Nam HW, Bruner RC, Choi DS. Adenosine signaling in striatal circuits and alcohol use disorders. Mol Cells. 2013;36(3):195-202. https://doi.org/10.1007/s10059-013-0192-9Naoi M, Maruyama W, Akao Y, Yi H. Dopaminederived endogenous N-methyl-(R)-salsolinol: its role in Parkinson’s disease. Neurotoxicol Teratol. 2002;24(5):579-591. https://doi.org/10.1016/s0892-0362(02)00211-8Naoi M, Maruyama W, Akao Y, Yi H. Dopaminederived endogenous N-methyl-(R)-salsolinol: its role in Parkinson’s disease. Neurotoxicol Teratol. 2002;24(5):579-591. https://doi.org/10.1016/s0892-0362(02)00211-8Nieto SJ, Grodin EN, Aguirre CG, Izquierdo A, Ray LA. Translational opportunities in animal and human models to study alcohol use disorder. Transl Psychiatry. 2021;11(1):496. https://doi.org/10.1038/s41398-021-01615-0Nieto SJ, Grodin EN, Aguirre CG, Izquierdo A, Ray LA. Translational opportunities in animal and human models to study alcohol use disorder. Transl Psychiatry. 2021;11(1):496. https://doi.org/10.1038/s41398-021-01615-0Noble EP. Alcoholism and the dopaminergic system: a review. Addict Biol. 1996;1(4):333-348. https://doi.org/10.1080/1355621961000124956Noble EP. Alcoholism and the dopaminergic system: a review. Addict Biol. 1996;1(4):333-348. https://doi.org/10.1080/1355621961000124956Oleson EB, Talluri S, Childers SR, Smith JE, Roberts D, Bonin KD, Budygin EA. Dopamine uptake changes associated with cocaine self-administration. Neuropsychopharmacology. 2009;34(5):1174-1184.Oleson EB, Talluri S, Childers SR, Smith JE, Roberts D, Bonin KD, Budygin EA. Dopamine uptake changes associated with cocaine self-administration. Neuropsychopharmacology. 2009;34(5):1174-1184.Owesson-White CA, Ariansen J, Stuber GD, Cleaveland NA, Cheer JF, Wightman RM, Carelli RM. Neural encoding of cocaine-seeking behavior is coincident with phasic dopamine release in the accumbens core and shell. Eur J Neurosci. 2009;30(6):1117-1127. https://doi.org/10.1111/j.1460-9568.2009.06916.xOwesson-White CA, Ariansen J, Stuber GD, Cleaveland NA, Cheer JF, Wightman RM, Carelli RM. Neural encoding of cocaine-seeking behavior is coincident with phasic dopamine release in the accumbens core and shell. Eur J Neurosci. 2009;30(6):1117-1127. https://doi.org/10.1111/j.1460-9568.2009.06916.xParsons LH, Justice JB, Jr. Extracellular concentration and in vivo recovery of dopamine in the nucleus accumbens using microdialysis. J Neurochem. 1992;58(1):212-218. https://doi.org/10.1111/j.1471-4159.1992.tb09298.xParsons LH, Justice JB, Jr. Extracellular concentration and in vivo recovery of dopamine in the nucleus accumbens using microdialysis. J Neurochem. 1992;58(1):212-218. https://doi.org/10.1111/j.1471-4159.1992.tb09298.xPatkar AA, Gopalakrishnan R, Naik PC, Murray HW, Vergare MJ, Marsden CA. Changes in plasma noradrenaline and serotonin levels and craving during alcohol withdrawal. Alcohol Alcohol. 2003;38(3):224-231. https://doi.org/10.1093/alcalc/agg055Patkar AA, Gopalakrishnan R, Naik PC, Murray HW, Vergare MJ, Marsden CA. Changes in plasma noradrenaline and serotonin levels and craving during alcohol withdrawal. Alcohol Alcohol. 2003;38(3):224-231. https://doi.org/10.1093/alcalc/agg055Phillips PE, Stuber GD, Heien ML, Wightman RM, Carelli RM. Subsecond dopamine release promotes cocaine seeking. Nature. 2003;422(6932):614-618.Phillips PE, Stuber GD, Heien ML, Wightman RM, Carelli RM. Subsecond dopamine release promotes cocaine seeking. Nature. 2003;422(6932):614-618.Riihioja P, Jaatinen P, Oksanen H, Haapalinna A, Heinonen E, Hervonen A. Dexmedetomidine, diazepam, and propranolol in the treatment of ethanol withdrawal symptoms in the rat. Alcohol Clin Exp Res. 1997;21(5):804-808.Riihioja P, Jaatinen P, Oksanen H, Haapalinna A, Heinonen E, Hervonen A. Dexmedetomidine, diazepam, and propranolol in the treatment of ethanol withdrawal symptoms in the rat. Alcohol Clin Exp Res. 1997;21(5):804-808.Robinson DL, Howard EC, McConnell S, Gonzales RA, Wightman RM. Disparity between tonic and phasic ethanol-induced dopamine increases in the nucleus accumbens of rats. Alcohol Clin Exp Res. 2009;33(7):1187-1196. https://doi.org/10.1111/j.1530-0277.2009.00942.xRobinson DL, Howard EC, McConnell S, Gonzales RA, Wightman RM. Disparity between tonic and phasic ethanol-induced dopamine increases in the nucleus accumbens of rats. Alcohol Clin Exp Res. 2009;33(7):1187-1196. https://doi.org/10.1111/j.1530-0277.2009.00942.xRodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li TK, Lumeng L, McBride WJ. Chronic ethanol drinking by alcohol-preferring rats increases the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol. Alcohol Clin Exp Res. 2005;29(3):358-366. https://doi.org/10.1097/01.alc.0000156127.30983.9dRodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li TK, Lumeng L, McBride WJ. Chronic ethanol drinking by alcohol-preferring rats increases the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol. Alcohol Clin Exp Res. 2005;29(3):358-366. https://doi.org/10.1097/01.alc.0000156127.30983.9dRodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li TK, Lumeng L, McBride WJ. Prolonged increase in the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol following repeated exposure to cycles of ethanol access and deprivation. J Pharmacol Exp Ther. 2005;315(2):648-657. https://doi.org/10.1124/jpet.105.084350Rodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li TK, Lumeng L, McBride WJ. Prolonged increase in the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol following repeated exposure to cycles of ethanol access and deprivation. J Pharmacol Exp Ther. 2005;315(2):648-657. https://doi.org/10.1124/jpet.105.084350Rodd ZA, Bell RL, Zhang Y, Goldstein A, Zaffaroni A, McBride WJ, Li TK. Salsolinol produces reinforcing effects in the nucleus accumbens shell of alcohol-preferring (P) rats. Alcohol Clin Exp Res. 2003;27(3):440-449. https://doi.org/10.1097/01.alc.0000056612.89957.b4Rodd ZA, Bell RL, Zhang Y, Goldstein A, Zaffaroni A, McBride WJ, Li TK. Salsolinol produces reinforcing effects in the nucleus accumbens shell of alcohol-preferring (P) rats. Alcohol Clin Exp Res. 2003;27(3):440-449. https://doi.org/10.1097/01.alc.0000056612.89957.b4Rommelfanger KS, Mitrano DA, Smith Y, Weinshenker D. Light and electron microscopic localization of alpha-1 adrenergic receptor immunoreactivity in the rat striatum and ventral midbrain. Neuroscience. 2009;158(4):1530-1540. https://doi.org/10.1016/j.neuroscience.2008.11.019Rommelfanger KS, Mitrano DA, Smith Y, Weinshenker D. Light and electron microscopic localization of alpha-1 adrenergic receptor immunoreactivity in the rat striatum and ventral midbrain. Neuroscience. 2009;158(4):1530-1540. https://doi.org/10.1016/j.neuroscience.2008.11.019Rossetti ZL, Longu G, Mercuro G, Hmaidan Y, Gessa GL. Biphasic effect of ethanol on noradrenaline release in the frontal cortex of awake rats. Alcohol Alcohol. 1992;27(5):477-480.Rossetti ZL, Longu G, Mercuro G, Hmaidan Y, Gessa GL. Biphasic effect of ethanol on noradrenaline release in the frontal cortex of awake rats. Alcohol Alcohol. 1992;27(5):477-480.Rothblat DS, Rubin E, Schneider J. Effects of chronic alcohol ingestion on the mesostriatal dopamine system in the rat. Neuroscience letters. 2001;300(2):63-66.Rothblat DS, Rubin E, Schneider J. Effects of chronic alcohol ingestion on the mesostriatal dopamine system in the rat. Neuroscience letters. 2001;300(2):63-66.Salinas AG, Mateo Y, Carlson VCC, Stinnett GS, Luo G, Seasholtz AF, Grant KA, Lovinger DM. Long-term alcohol consumption alters dorsal striatal dopamine release and regulation by D2 dopamine receptors in rhesus macaques. Neuropsychopharmacology. 2021;46(8):1432-1441. https://doi.org/10.1038/s41386-020-00938-8Salinas AG, Mateo Y, Carlson VCC, Stinnett GS, Luo G, Seasholtz AF, Grant KA, Lovinger DM. Long-term alcohol consumption alters dorsal striatal dopamine release and regulation by D2 dopamine receptors in rhesus macaques. Neuropsychopharmacology. 2021;46(8):1432-1441. https://doi.org/10.1038/s41386-020-00938-8Samson HH, Chappell AM. Effects of raclopride in the core of the nucleus accumbens on ethanol seeking and consumption: the use of extinction trials to measure seeking. Alcohol Clin Exp Res. 2004;28(4):544-549. https://doi.org/10.1097/01.alc.0000121649.81642.3fSamson HH, Chappell AM. Effects of raclopride in the core of the nucleus accumbens on ethanol seeking and consumption: the use of extinction trials to measure seeking. Alcohol Clin Exp Res. 2004;28(4):544-549. https://doi.org/10.1097/01.alc.0000121649.81642.3fSamson HH, Czachowski CL. Behavioral measures of alcohol self-administration and intake control: rodent models. Int Rev Neurobiol. 2003;54:107-143. https://doi.org/10.1016/s0074-7742(03)54004-1Samson HH, Czachowski CL. Behavioral measures of alcohol self-administration and intake control: rodent models. Int Rev Neurobiol. 2003;54:107-143. https://doi.org/10.1016/s0074-7742(03)54004-1Sango K, Maruyama W, Matsubara K, Dostert P, Minami C, Kawai M, Naoi M. Enantio-selective occurrence of (S)-tetrahydropapaveroline in human brain. Neurosci Lett. 2000;283(3):224-246. https://doi.org/10.1016/s0304-3940(00)00963-0Sango K, Maruyama W, Matsubara K, Dostert P, Minami C, Kawai M, Naoi M. Enantio-selective occurrence of (S)-tetrahydropapaveroline in human brain. Neurosci Lett. 2000;283(3):224-246. https://doi.org/10.1016/s0304-3940(00)00963-0Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci. 2009;10(3):211-23. https://doi.org/10.1038/nrn2573Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci. 2009;10(3):211-23. https://doi.org/10.1038/nrn2573Sara SJ, Bouret S. Orienting and reorienting: the locus coeruleus mediates cognition through arousal. Neuron. 2012;76(1):130-141. https://doi.org/10.1016/j.neuron.2012.09.011Sara SJ, Bouret S. Orienting and reorienting: the locus coeruleus mediates cognition through arousal. Neuron. 2012;76(1):130-141. https://doi.org/10.1016/j.neuron.2012.09.011Schulteis G, Markou A, Cole M, Koob GF. Decreased brain reward produced by ethanol withdrawal. Proc Natl Acad Sci U S A. 1995;92(13):5880-5884. https://doi.org/10.1073/pnas.92.13.5880Schulteis G, Markou A, Cole M, Koob GF. Decreased brain reward produced by ethanol withdrawal. Proc Natl Acad Sci U S A. 1995;92(13):5880-5884. https://doi.org/10.1073/pnas.92.13.5880Schultz W. Predictive reward signal of dopamine neurons. J Neurophysiol. 1998;80(1):1-27. https://doi.org/10.1152/jn.1998.80.1.1Schultz W. Predictive reward signal of dopamine neurons. J Neurophysiol. 1998;80(1):1-27. https://doi.org/10.1152/jn.1998.80.1.1Siggins GR, Roberto M, Nie Z. The tipsy terminal: presynaptic effects of ethanol. Pharmacol Ther. 2005;107(1):80-98. https://doi.org/10.1016/j.pharmthera.2005.01.006Siggins GR, Roberto M, Nie Z. The tipsy terminal: presynaptic effects of ethanol. Pharmacol Ther. 2005;107(1):80-98. https://doi.org/10.1016/j.pharmthera.2005.01.006Simms I, Broutet N. Congenital syphilis re-emerging. J Dtsch Dermatol Ges. 2008;6(4):269-272. https://doi.org/10.1111/j.1610-0387.2008.06490.xSimms I, Broutet N. Congenital syphilis re-emerging. J Dtsch Dermatol Ges. 2008;6(4):269-272. https://doi.org/10.1111/j.1610-0387.2008.06490.xSimpson TL, Saxon AJ, Meredith CW, Malte CA, McBride B, Ferguson LC, Gross CA, Hart KL, Raskind M. A pilot trial of the alpha-1 adrenergic antagonist, prazosin, for alcohol dependence. Alcohol Clin Exp Res. 2009;33(2):255-263. https://doi.org/10.1111/j.1530-0277.2008.00807.xSimpson TL, Saxon AJ, Meredith CW, Malte CA, McBride B, Ferguson LC, Gross CA, Hart KL, Raskind M. A pilot trial of the alpha-1 adrenergic antagonist, prazosin, for alcohol dependence. Alcohol Clin Exp Res. 2009;33(2):255-263. https://doi.org/10.1111/j.1530-0277.2008.00807.xSmith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150(1):76-85. https://doi.org/10.1016/0003-2697(85)90442-7Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150(1):76-85. https://doi.org/10.1016/0003-2697(85)90442-7Söderpalm B, Ericson M. Neurocircuitry involved in the development of alcohol addiction: the dopamine system and its access points. Curr Top Behav Neurosci. 2013;13:127-161. https://doi.org/10.1007/7854_2011_170Söderpalm B, Ericson M. Neurocircuitry involved in the development of alcohol addiction: the dopamine system and its access points. Curr Top Behav Neurosci. 2013;13:127-161. https://doi.org/10.1007/7854_2011_170Steensland P, Fredriksson I, Holst S, Feltmann K, Franck J, Schilström B, Carlsson A. The monoamine stabilizer (-)-OSU6162 attenuates voluntary ethanol intake and ethanol-induced dopamine output in nucleus accumbens. Biol Psychiatry. 2012;72(10):823-831. https://doi.org/10.1016/j.biopsych.2012.06.018Steensland P, Fredriksson I, Holst S, Feltmann K, Franck J, Schilström B, Carlsson A. The monoamine stabilizer (-)-OSU6162 attenuates voluntary ethanol intake and ethanol-induced dopamine output in nucleus accumbens. Biol Psychiatry. 2012;72(10):823-831. https://doi.org/10.1016/j.biopsych.2012.06.018Steinberg EE, Keiflin R, Boivin JR, Witten IB, Deisseroth K, Janak PH. A causal link between prediction errors, dopamine neurons and learning. Nature neuroscience. 2013;16(7):966-973.Steinberg EE, Keiflin R, Boivin JR, Witten IB, Deisseroth K, Janak PH. A causal link between prediction errors, dopamine neurons and learning. Nature neuroscience. 2013;16(7):966-973.Szabadi E. Functional neuroanatomy of the central noradrenergic system. J Psychopharmacol. 2013;27(8):659-693. https://doi.org/10.1177/0269881113490326Szabadi E. Functional neuroanatomy of the central noradrenergic system. J Psychopharmacol. 2013;27(8):659-693. https://doi.org/10.1177/0269881113490326Tang A, George MA, Randall JA, Gonzales RA. Ethanol increases extracellular dopamine concentration in the ventral striatum in C57BL/6 mice. Alcohol Clin Exp Res. 2003;27(7):1083-1089. https://doi.org/10.1097/01.alc.0000075825.14331.65Tang A, George MA, Randall JA, Gonzales RA. Ethanol increases extracellular dopamine concentration in the ventral striatum in C57BL/6 mice. Alcohol Clin Exp Res. 2003;27(7):1083-1089. https://doi.org/10.1097/01.alc.0000075825.14331.65Thanos PK, Volkow ND, Freimuth P, Umegaki H, Ikari H, Roth G, Ingram DK, Hitzemann R. Overexpression of dopamine D2 receptors reduces alcohol self-administration. J Neurochem. 2001;78(5):1094-1103. https://doi.org/10.1046/j.1471-4159.2001.00492.xThanos PK, Volkow ND, Freimuth P, Umegaki H, Ikari H, Roth G, Ingram DK, Hitzemann R. Overexpression of dopamine D2 receptors reduces alcohol self-administration. J Neurochem. 2001;78(5):1094-1103. https://doi.org/10.1046/j.1471-4159.2001.00492.xThiele TE, Marsh DJ, Ste Marie L, Bernstein IL, Palmiter RD. Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature. 1998;396(6709):366-369. https://doi.org/10.1038/24614Thiele TE, Marsh DJ, Ste Marie L, Bernstein IL, Palmiter RD. Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature. 1998;396(6709):366-369. https://doi.org/10.1038/24614Trzaskowska E, Puciłowski O, Dyr W, Kostowski W, Hauptmann M. Suppression of ethanol tolerance and dependence in rats treated with DSP-4, a noradrenergic neurotoxin. Drug Alcohol Depend. 1986;18(4):349-353. https://doi.org/10.1016/0376-8716(86)90098-0Trzaskowska E, Puciłowski O, Dyr W, Kostowski W, Hauptmann M. Suppression of ethanol tolerance and dependence in rats treated with DSP-4, a noradrenergic neurotoxin. Drug Alcohol Depend. 1986;18(4):349-353. https://doi.org/10.1016/0376-8716(86)90098-0Tsai HC, Zhang F, Adamantidis A, Stuber GD, Bonci A, de Lecea L, Deisseroth K. Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science. 2009;324(5930):1080-1084. https://doi.org/10.1126/science.1168878Tsai HC, Zhang F, Adamantidis A, Stuber GD, Bonci A, de Lecea L, Deisseroth K. Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science. 2009;324(5930):1080-1084. https://doi.org/10.1126/science.1168878Tucker JA, Chandler SD, Witkiewitz K. Epidemiology of Recovery From Alcohol Use Disorder. Alcohol Res. 2020;40(3):02. https://doi.org/10.35946/arcr.v40.3.02Tucker JA, Chandler SD, Witkiewitz K. Epidemiology of Recovery From Alcohol Use Disorder. Alcohol Res. 2020;40(3):02. https://doi.org/10.35946/arcr.v40.3.02Tupala E, Hall H, Bergström K, Särkioja T, Räsänen P, Mantere T, Callaway J, Hiltunen J, Tiihonen J. Dopamine D(2)/D(3)-receptor and transporter densities in nucleus accumbens and amygdala of type 1 and 2 alcoholics. Mol Psychiatry. 2001;6(3):261-267. https://doi.org/10.1038/sj.mp.4000859Tupala E, Hall H, Bergström K, Särkioja T, Räsänen P, Mantere T, Callaway J, Hiltunen J, Tiihonen J. Dopamine D(2)/D(3)-receptor and transporter densities in nucleus accumbens and amygdala of type 1 and 2 alcoholics. Mol Psychiatry. 2001;6(3):261-267. https://doi.org/10.1038/sj.mp.4000859Valentino RJ, Van Bockstaele E. Convergent regulation of locus coeruleus activity as an adaptive response to stress. Eur J Pharmacol. 2008;583(2-3):194-203. https://doi.org/10.1016/j.ejphar.2007.11.062Valentino RJ, Van Bockstaele E. Convergent regulation of locus coeruleus activity as an adaptive response to stress. Eur J Pharmacol. 2008;583(2-3):194-203. https://doi.org/10.1016/j.ejphar.2007.11.062Vankov A, Hervé-Minvielle A, Sara SJ. Response to novelty and its rapid habituation in locus coeruleus neurons of the freely exploring rat. Eur J Neurosci. 1995;7(6):1180-1187. https://doi.org/10.1111/j.1460-9568.1995.tb01108.xVankov A, Hervé-Minvielle A, Sara SJ. Response to novelty and its rapid habituation in locus coeruleus neurons of the freely exploring rat. Eur J Neurosci. 1995;7(6):1180-1187. https://doi.org/10.1111/j.1460-9568.1995.tb01108.xVazey EM, Moorman DE, Aston-Jones G. Phasic locus coeruleus activity regulates cortical encoding of salience information. Proc Natl Acad Sci USA. 2018;115(40):E9439-e9448. https://doi.org/10.1073/pnas.1803716115Vazey EM, Moorman DE, Aston-Jones G. Phasic locus coeruleus activity regulates cortical encoding of salience information. Proc Natl Acad Sci USA. 2018;115(40):E9439-e9448. https://doi.org/10.1073/pnas.1803716115Vena AA, Zandy SL, Cofresí RU, Gonzales RA. Behavioral, neurobiological, and neurochemical mechanisms of ethanol self-administration: A translational review. Pharmacol Ther. 2020;212:107573. https://doi.org/10.1016/j.pharmthera.2020.107573Vena AA, Zandy SL, Cofresí RU, Gonzales RA. Behavioral, neurobiological, and neurochemical mechanisms of ethanol self-administration: A translational review. Pharmacol Ther. 2020;212:107573. https://doi.org/10.1016/j.pharmthera.2020.107573Volkow ND, Wang GJ, Begleiter H, Porjesz B, Fowler JS, Telang F, Wong C, Ma Y, Logan J, Goldstein R, Alexoff D, Thanos PK. High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. Arch Gen Psychiatry. 2006;63(9):999-1008. https://doi.org/10.1001/archpsyc.63.9.999Volkow ND, Wang GJ, Begleiter H, Porjesz B, Fowler JS, Telang F, Wong C, Ma Y, Logan J, Goldstein R, Alexoff D, Thanos PK. High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. Arch Gen Psychiatry. 2006;63(9):999-1008. https://doi.org/10.1001/archpsyc.63.9.999Volkow ND, Wang GJ, Fowler JS, Logan J, Hitzemann R, Ding YS, Pappas N, Shea C, Piscani K. Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin Exp Res. 1996;20(9):1594-1598. https://doi.org/10.1111/j.1530-0277.1996.tb05936.xVolkow ND, Wang GJ, Fowler JS, Logan J, Hitzemann R, Ding YS, Pappas N, Shea C, Piscani K. Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin Exp Res. 1996;20(9):1594-1598. https://doi.org/10.1111/j.1530-0277.1996.tb05936.xVolkow ND, Wang GJ, Fowler JS, Tomasi D, Telang F, Baler R. Addiction: decreased rewardsensitivity and increased expectation sensitivity conspire to overwhelm the brain’s control circuit. Bioessays. 2010;32(9):748-755. https://doi.org/10.1002/bies.201000042Volkow ND, Wang GJ, Fowler JS, Tomasi D, Telang F, Baler R. Addiction: decreased rewardsensitivity and increased expectation sensitivity conspire to overwhelm the brain’s control circuit. Bioessays. 2010;32(9):748-755. https://doi.org/10.1002/bies.201000042Walinder J, Balldin J, Bokstrom K, Karlsson I, Lundstrom B, Svensson TH. Clonidine suppression of the alcohol withdrawal syndrome. Drug Alcohol Depend. 1981;8(4):345-348. https://doi.org/10.1016/0376-8716(81)90043-0Walinder J, Balldin J, Bokstrom K, Karlsson I, Lundstrom B, Svensson TH. Clonidine suppression of the alcohol withdrawal syndrome. Drug Alcohol Depend. 1981;8(4):345-348. https://doi.org/10.1016/0376-8716(81)90043-0Walker BM, Rasmussen DD, Raskind MA, Koob GF. alpha1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol. Alcohol. 2008;42(2):91-97. https://doi.org/10.1016/j.alcohol.2007.12.002Walker BM, Rasmussen DD, Raskind MA, Koob GF. alpha1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol. Alcohol. 2008;42(2):91-97. https://doi.org/10.1016/j.alcohol.2007.12.002Weinshenker D, Rust NC, Miller NS, Palmiter RD. Ethanol-associated behaviors of mice lacking norepinephrine. J Neurosci. 2000;20(9):3157-3164. 10.1523/jneurosci.20-09-03157.2000Weinshenker D, Rust NC, Miller NS, Palmiter RD. Ethanol-associated behaviors of mice lacking norepinephrine. J Neurosci. 2000;20(9):3157-3164. 10.1523/jneurosci.20-09-03157.2000Weiss F, Parsons LH, Schulteis G, Hyytiä P, Lorang MT, Bloom FE, Koob GF. Ethanol selfadministration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci. 1996;16(10):3474-3485. https://doi.org/10.1523/jneurosci.16-10-03474.1996Weiss F, Parsons LH, Schulteis G, Hyytiä P, Lorang MT, Bloom FE, Koob GF. Ethanol selfadministration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci. 1996;16(10):3474-3485. https://doi.org/10.1523/jneurosci.16-10-03474.1996Weiss F, Porrino LJ. Behavioral neurobiology of alcohol addiction: recent advances and challenges. J Neurosci. 2002;22(9):3332-3337. https://doi.org/10.1523/jneurosci.22-09-03332.2002Weiss F, Porrino LJ. Behavioral neurobiology of alcohol addiction: recent advances and challenges. J Neurosci. 2002;22(9):3332-3337. https://doi.org/10.1523/jneurosci.22-09-03332.2002West CH, Boss-Williams KA, Ritchie JC, Weiss JM. Reprint of: Locus coeruleus neuronal activity determines proclivity to consume alcohol in a selectively-bred line of rats that readily consumes alcohol. Alcohol. 2016;50:91-105. https://doi.org/10.1016/j.alcohol.2016.01.001West CH, Boss-Williams KA, Ritchie JC, Weiss JM. Reprint of: Locus coeruleus neuronal activity determines proclivity to consume alcohol in a selectively-bred line of rats that readily consumes alcohol. Alcohol. 2016;50:91-105. https://doi.org/10.1016/j.alcohol.2016.01.001West MW, Biggs TA, Tavares E, Lankford MF, Myers RD. Drinking patterns in genetic low-alcohol- drinking (LAD) rats after systemic cyanamide and cerebral injections of THP or 6-OHDA. Alcohol. 1998;15(3):239-247. https://doi.org/10.1016/s0741-8329(97)00126-2West MW, Biggs TA, Tavares E, Lankford MF, Myers RD. Drinking patterns in genetic low-alcohol- drinking (LAD) rats after systemic cyanamide and cerebral injections of THP or 6-OHDA. Alcohol. 1998;15(3):239-247. https://doi.org/10.1016/s0741-8329(97)00126-2Wightman RM, Robinson DL. Transient changes in mesolimbic dopamine and their association with ‘reward’. J Neurochem. 2002;82(4):721-735. https://doi.org/10.1046/j.1471-4159.2002.01005.xWightman RM, Robinson DL. Transient changes in mesolimbic dopamine and their association with ‘reward’. J Neurochem. 2002;82(4):721-735. https://doi.org/10.1046/j.1471-4159.2002.01005.xWightman RM, Zimmerman JB. Control of dopamine extracellular concentration in rat striatum by impulse flow and uptake. Brain Res Brain Res Rev. 1990;15(2):135-144. https://doi.org/10.1016/0165-0173(90)90015-gWightman RM, Zimmerman JB. Control of dopamine extracellular concentration in rat striatum by impulse flow and uptake. Brain Res Brain Res Rev. 1990;15(2):135-144. https://doi.org/10.1016/0165-0173(90)90015-gWise RA. Maximization of ethanol intake in the rat. Adv Exp Med Biol. 1975;59:279-294. https://doi.org/10.1007/978-1-4757-0632-1_19Wise RA. Maximization of ethanol intake in the rat. Adv Exp Med Biol. 1975;59:279-294. https://doi.org/10.1007/978-1-4757-0632-1_19Witten IB, Steinberg EE, Lee SY, Davidson TJ, Zalocusky KA, Brodsky M, Yizhar O, Cho SL, Gong S, Ramakrishnan C, Stuber GD, Tye KM, Janak PH, Deisseroth K. Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement. Neuron. 2011;72(5):721-733. https://doi.org/10.1016/j.neuron.2011.10.028Witten IB, Steinberg EE, Lee SY, Davidson TJ, Zalocusky KA, Brodsky M, Yizhar O, Cho SL, Gong S, Ramakrishnan C, Stuber GD, Tye KM, Janak PH, Deisseroth K. Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement. Neuron. 2011;72(5):721-733. https://doi.org/10.1016/j.neuron.2011.10.028Woodward JJ. Ethanol and NMDA receptor signaling. Crit Rev Neurobiol. 2000;14(1):69-89. https://doi.org/10.1080/08913810008443548Woodward JJ. Ethanol and NMDA receptor signaling. Crit Rev Neurobiol. 2000;14(1):69-89. https://doi.org/10.1080/08913810008443548Wu R, Liu J, Wang K, Huang Y, Zhang Y, Li JX. Effects of a trace amine-associated receptor 1 agonist RO 5263397 on ethanol-induced behavioral sensitization. Behav Brain Res. 2020;390:112641. https://doi.org/10.1016/j.bbr.2020.112641Wu R, Liu J, Wang K, Huang Y, Zhang Y, Li JX. Effects of a trace amine-associated receptor 1 agonist RO 5263397 on ethanol-induced behavioral sensitization. Behav Brain Res. 2020;390:112641. https://doi.org/10.1016/j.bbr.2020.112641Xie G, Kresimir K, Ye J-H. Salsolinol modulation of dopamine neurons. Frontiers Behav Neurosci. 2013; 7(52):1-7. https://doi.org/10.3389/fnbeh.2013.00052160Xie G, Kresimir K, Ye J-H. Salsolinol modulation of dopamine neurons. Frontiers Behav Neurosci. 2013; 7(52):1-7. https://doi.org/10.3389/fnbeh.2013.00052160Ye L, Orynbayev M, Zhu X, Lim EY, Dereddi RR, Agarwal A, Bergles DE, Bhat MA, Paukert M. Ethanol abolishes vigilance-dependent astroglia network activation in mice by inhibiting norepinephrine release. Nat Commun. 2020;11(1):6157. https://doi.org/10.1038/s41467-020-19475-5Ye L, Orynbayev M, Zhu X, Lim EY, Dereddi RR, Agarwal A, Bergles DE, Bhat MA, Paukert M. Ethanol abolishes vigilance-dependent astroglia network activation in mice by inhibiting norepinephrine release. Nat Commun. 2020;11(1):6157. https://doi.org/10.1038/s41467-020-19475-5Zimatkin SM, Deitrich RA. Ethanol metabolism in the brain. Addict Biol. 1997;2(4):387-400. https://doi.org/10.1080/13556219772444Zimatkin SM, Deitrich RA. Ethanol metabolism in the brain. Addict Biol. 1997;2(4):387-400. https://doi.org/10.1080/13556219772444

The authors declare that there are no conflicts of interest present.