Abstract
The brain reward system, and especially the mesolimbic dopamine pathway, plays a major role in drug reinforcement and is most likely involved in the development of drug addiction. All major drugs of abuse, including ethanol, acutely activate the mesolimbic dopamine system. Both this acute drug-induced dopamine elevation, the dopamine elevations observed after presentations of drug-associated stimuli and alterations of dopamine function induced by chronic drug administration are of importance. Whereas the mechanisms of actions for central stimulants, opioids and nicotine in their dopamine activating effects are fairly well established, the corresponding mechanisms with respect to ethanol have been elusive. Here we review the actions of ethanol in the mesolimbic dopamine system, focusing on ethanol’s interaction with ligand-gated ion-channel receptors, opiate receptors, the ghrelin system and the possible involvement of acetaldehyde. Preclinical studies have provided the opportunity to dissect these interactions in some detail and although we do not fully comprehend the actions of ethanol there have been some great advances resulting in increased knowledge of the complexity of ethanol’s mechanism of action in this system.
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Abbreviations
- 5-HT:
-
Serotonin
- ACTH:
-
Adrenocorticotrophic hormone
- ADHD:
-
Attention-Deficit/Hyperactivity Disorder
- AMPA:
-
2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid
- GABA:
-
Gamma-aminobutyric acid
- GHS-R:
-
Growth hormone secretagogue receptor
- GlyR:
-
Glycine receptor
- nAc:
-
Nucleus accumbens
- nAChR:
-
Nicotinic acetylcholine receptor
- NMDA:
-
n-methyl-d-aspartate
- NR1/2:
-
NMDA receptor one/two
- rt-PCR:
-
Reverse transcriptase polymerase chain reaction
- VTA:
-
Ventral tegmental area
References
Acquas E, Meloni M, Di Chiara G (1993) Blockade of delta-opioid receptors in the nucleus accumbens prevents ethanol-induced stimulation of dopamine release. Eur J Pharmacol 230(2):239–241
Addolorato G, Capristo E, Leggio L, Ferrulli A, Abenavoli L, Malandrino N, Farnetti S, Domenicali M, D’Angelo C, Vonghia L, Mirijello A, Cardone S, Gasbarrini G (2006) Relationship between ghrelin levels, alcohol craving, and nutritional status in current alcoholic patients. Alcohol Clin Exp Res 30(11):1933–1937
Adermark L, Clarke RBC, Olsson T, Hansson E, Söderpalm B, Ericson M (2011) Implications for glycine receptors and astrocytes in ethanol-induced elevation of dopamine levels in the nucleus accumbens. Addict Biol 16(1):43–54
Aguayo LG, Pancetti FC (1994) Ethanol modulation of the gamma-aminobutyric acidA- and glycine-activated Cl- current in cultured mouse neurons. J Pharmacol Exp Ther 270(1):61–69
Aguayo LG, Tapia JC, Pancetti FC (1996) Potentiation of the glycine-activated Cl- current by ethanol in cultured mouse spinal neurons. J Pharmacol Exp Ther 279(3):1116–1122
Ahlenius S, Carlsson A, Engel J, Svensson T, Sodersten P (1973) Antagonism by alpha methyltyrosine of the ethanol-induced stimulation and euphoria in man. Clin Pharmacol Ther 14(4):586–591
Ahmed SH, Koob GF (2005) Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function. Psychopharmacology (Berl) 180(3):473–490
Aistrup GL, Marszalec W, Narahashi T (1999) Ethanol modulation of nicotinic acetylcholine receptor currents in cultured cortical neurons. Mol Pharmacol 55(1):39–49
Altshuler HL, Phillips PE, Feinhandler DA (1980) Alteration of ethanol self-administration by naltrexone. Life Sci 26(9):679–688
Amit Z, Brown ZW, Rockman GE (1977) Possible involvement of acetaldehyde, norepinephrine and their tetrahydroisoquinoline derivatives in the regulation of ethanol seld-administration. Drug Alcohol Depend 2:495–500
Benjamin D, Grant ER, Pohorecky LA (1993) Naltrexone reverses ethanol-induced dopamine release in the nucleus accumbens in awake, freely moving rats. Brain Res 621(1):137–140
Betz H (1992) Structure and function of inhibitory glycine receptors. Q Rev Biophys 25(4):381–394
Blaha CD, Yang CR, Floresco SB, Barr AM, Phillips AG (1997) Stimulation of the ventral subiculum of the hippocampus evokes glutamate receptor-mediated changes in dopamine efflux in the rat nucleus accumbens. Eur J Neurosci 9(5):902–911
Blomqvist O, Engel JA, Nissbrandt H, Soderpalm B (1993) The mesolimbic dopamine-activating properties of ethanol are antagonized by mecamylamine. Eur J Pharmacol 249(2):207–213
Blomqvist O, Ericson M, Engel JA, Söderpalm B (1997) Accumbal dopamine overflow after ethanol: localization of the antagonizing effect of mecamylamine. Eur J Pharmacol 334(2–3):149–156
Blomqvist O, Ericson M, Johnson DH, Engel JA, Söderpalm B (1996) Voluntary ethanol intake in the rat: effects of nicotinic acetylcholine receptor blockade or subchronic nicotine treatment. Eur J Pharmacol 314:257–267
Blomqvist O, Hernandez-Avila CA, Van Kirk J, Rose JE, Kranzler HR (2002) Mecamylamine modifies the pharmacokinetics and reinforcing effects of alcohol. Alcohol Clin Exp Res 26:326–331
Blomqvist O, Söderpalm B, Engel JA (1992) Ethanol-induced locomotor activity: involvement of central nicotinic acetylcholine receptors? Brain Res Bull 29(2):173–178
Boileau I, Assaad JM, Pihl RO, Benkelfat C, Leyton M, Diksic M, Tremblay RE, Dagher A (2003) Alcohol promotes dopamine release in the human nucleus accumbens. Synapse 49:226–231
Boismare F, Daoust M, Moore N, Saligaut C, Lhuintre JP, Chretien P, Durlach J (1984) A homotaurine derivative reduces the voluntary intake of ethanol by rats: are cerebral GABA receptors involved? Pharmacol Biochem Behav 21(5):787–789
Borghese CM, Henderson LA, Bleck V, Trudell JR, Harris RA (2003a) Sites of excitatory and inhibitory actions of alcohols on neuronal alpha2beta4 nicotinic acetylcholine receptors. J Pharmacol Exp Ther 307(1):42–52
Borghese CM, Wang L, Bleck V, Harris RA (2003b) Mutation in neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes blocks ethanol action. Addict Biol 8(3):313–318
Bourdélat-Parks BN, Anderson GM, Donaldson ZR, Weiss JM, Bonsall RW, Emery MS et al (2005) Effects of dopamine beta-hydroxylase genotype and disulfiram inhibition on catecholamine homeostasis in mice. Psychopharmacology 183:72–80
Brackmann M, Zhao C, Schmieden V, Braunewell KH (2004) Cellular and subcellular localization of the inhibitory glycine receptor in hippocampal neurons. Biochem Biophys Res Commun 324(3):1137–1142
Bradley RJ, Peper K, Sterz R (1980) Postsynaptic effects of ethanol at the frog neuromuscular junction. Nature 284:60–62
Brunzell DH, Chang JR, Schneider B, Olausson P, Taylor JR, Picciotto MR (2006) Beta2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice. Psychopharmacology (Berl) 184(3–4):328–338
Burch JB, de Fiebre CM, Marks MJ, Collins AC (1988) Chronic ethanol or nicotine treatment results in partial cross-tolerance between these agents. Psychopharmacology (Berl) 95(4):452–458
Calissendorff J, Danielsson O, Brismar K, Röjdmark S (2005) Inhibitory effect of alcohol on ghrelin secretion in normal man. Eur J Endocrinol 152(5):743–747
Campbell AD, McBride WJ (1995) Serotonin-3 receptor and ethanol-stimulated dopamine release in the nucleus accumbens. Pharmacol Biochem Behav 51:835–842
Carboni E, Acquas E, Frau R, Di Chiara G (1989) Differential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release. Eur J Pharmacol 164:515–519
Cardoso RA, Brozowski SJ, Chavez-Noriega LE, Harpold M, Valenzuela CF, Harris RA (1999) Effects of ethanol on recombinant human neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. J Pharmacol Exp Ther 289(2):774–780
Carlsson A, Engel J, Svensson TH (1972) Inhibition of ethanol-induced excitation in mice and rats by α-methyl-p-tyrosine. Psychopharmacological 26(3):307–312
Carlsson A, Lindqvist M (1973) Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J Pharm Pharmacol 25:437–440
Carlsson A, Lindqvist M, Magnusson T (1957) 3, 4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180:1200
Carlsson A, Lindqvist M, Magnusson T, Waldeck B (1958) On the presence of 3-hydroxytyramine in brain. Science 127(3296):471
Celentano JJ, Gibbs TT, Farb DH (1988) Ethanol potentiates GABA- and glycine-induced chloride currents in chick spinal cord neurons. Brain Res 455(2):377–380
Chandler LJ, Sumners C, Crews FT (1993) Ethanol inhibits NMDA receptor-mediated excitotoxicity in rat primary neuronal cultures. Alcohol Clin Exp Res 17:54–60
Chattipakorn SC, McMahon LL (2003) Strychnine-sensitive glycine receptors depress hyperexcitability in rat dentate gyrus. J Neurophysiol 89(3):1339–1342
Chau P, Lidö HH, Söderpalm B, Ericson M (2010a) Glycine receptors in the nucleus accumbens involved in the ethanol intake-reducing effect of acamprosate. Alcohol Clin Exp Res 34(1):39–45
Chau P, Stomberg R, Löf E, Söderpalm B, Ericson M (2010b) Glycine receptors involved in acamprosate’s modulation of accumbal dopamine levels: an in vivo microdialysis study. Alcohol Clin Exp Res 34(1):32–28
Chen JP, van Praag HM, Gardner EL (1991) Activation of 5-HT3 receptor by 1-phenylbiguanide increases dopamine release in the rat nucleus accumbens. Brain Res 543:354–357
Chesnoy-Marchais D (1996) Potentiation of chloride responses to glycine by three 5-HT3 antagonists in rat spinal neurones. Br J Pharmacol 118:2115–2125
Chesnoy-Marchais D, Lévi S, Acher F (2000) Glycinergic potentiation by some 5-HT(3) receptor antagonists: insight into selectivity. Eur J Pharmacol 402:205–213
Chi H, de Wit H (2003) Mecamylamine attenuates the subjective stimulant-like effects of alcohol in social drinkers. Alcohol Clin Exp Res 27:780–786
Collins AC, Burch JB, de Fiebre CM, Marks MJ (1988) Tolerance to and cross tolerance between ethanol and nicotine. Pharmacol Biochem Behav 29(2):365–373
Corrigall WA, Coen KM, Adamson KL (1994) Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res 653(1–2):278–284
Corrodi H, Fuxe K, Hökfelt T (1966) The effect of ethanol on the activity of central catecholamine neurones in rat brain. J Pharm Pharmacol 18:821–823
Covernton PJ, Connolly JG (1997) Differential modulation of rat neuronal nicotinic receptor subtypes by acute application of ethanol. Br J Pharmacol 122(8):1661–1668
Criswell HE, Simson PE, Duncan GE, McCown TJ, Herbert JS, Morrow AL, Breese GE (1993) Molecular basis for regionally specific action of ethanol on g-aminobutyric acidA receptors: generalization to other ligand-gated ion channels. J Pharmacol Exp Ther 267:522–537
Czachowski CL, Chappell AM, Samson HH (2001) Effects of raclopride in the nucleus accumbens on ethanol seeking and consumption. Alcohol Clin Exp Res 25:1431–1440
Dahchour A, De Witte P, Bolo N, Nédélec JF, Muzet M, Durbin P, Macher JP (1998) Central effects of acamprosate: part 1. Acamprosate blocks the glutamate increase in the nucleus accumbens microdialysate in ethanol withdrawn rats. Psychiatry Res 82(2):107–114
Dahchour A, Quertemont E, De Witte P (1996) Taurine increases in the nucleus accumbens microdialysate after acute ethanol administration to naive and chronically alcoholised rats. Brain Res 735(1):9–19
Dahlström A, Fuxe K (1964) Localization of monoamines in the lower brain stem. Experientia 20:398–399
Davidson M, Wilce PA, Shanley BC (1993) Chronic ethanol administration sensitizes hippocampal neurons to neurotoxicity of N-methyl-D-aspartic acid. Alcohol Alcohol Suppl 2:365–369
Deitrich RA (2004) Acetaldehyde: deja vu du jour. J Stud Alcohol 65:557–572
Deng C, Li KY, Zhou C, Ye JH (2009) Ethanol enhances glutamate transmission by retrograde dopamine signaling in a postsynaptic neuron/synaptic bouton preparation from the ventral tegmental area. Neuropsychopharmacology 34(5):1233–1244
Diana M, Pistis M, Carboni S, Gessa GL, Rossetti ZL (1993) Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: electrophysiological and biochemical evidence. Proc Natl Acad Sci U S A 90(17):7966–7969
DiChiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A 85:5274–5278
DiChiara G, Imperato A (1985) Ethanol preferentially stimulates dopamine release in the nucleus accumbens of freely moving rats. Eur J Pharmacol 115(1):131–132
Dyr W, Koros E, Bienkowski P, Kostowski W (1999) Involvement of nicotinic acetylcholine receptors in the regulation of alcohol dringking in Wistar rats. Alcohol Alcohol 34(1):43–47
Edenberg HJ (2007) The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res Health 30:5–13
Ei-Fakahany EF, Miller ER, Abbassy MA, Eldefrawi AT, Eldefrawi ME (1983) Alcohol modulation of drug binding to the channel sites of the nicotinic acetylcholine receptor. J Pharmacol Exp Ther 224(2):289–296
Engblom AC, Akerman KE (1991) Effect of ethanol on gamma-aminobutyric acid and glycine receptor-coupled Cl- fluxes in rat brain synaptoneurosomes. J Neurochem 57(2):384–390
Engel J, Carlsson A (1977) Catecholamines and behavior. In: Valzelli L, Essman WB (eds) Current developments in psychopharmacology, vol 4. Spectrum Publishing, New York, pp 1–32
Engel J (1977) Neurochemical aspects of the euphoria induced by dependence-producing drugs. In: Recent advances in the Study of Alcoholism. (Excerpta Medunca International Congress Series 407). Excerpta Medica, Amsterdam, pp 16–22
Epping-Jordan MP, Watkins SS, Koob GF, Markou A (1998) Dramatic decreases in brain reward function during nicotine withdrawal. Nature 393(6680):76–79
Ericson M, Blomqvist O, Engel J, Söderpalm B (1998) Voluntary ethanol intake in the rat and the associated accumbal dopamine overflow are blocked by ventral tegmental mecamylamine. Eur J Pharmacol 358:189–196
Ericson M, Chau P, Clarke RB, Adermark L, Söderpalm B (2011) Rising taurine and ethanol concentrations in nucleus accumbens interact to produce dopamine release after ethanol administration. Addict Biol 16(3):377–385
Ericson M, Clarke R, Chau P, Adermark L, Söderpalm B (2010) β-alanine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. Amino Acids 38(4):1051–1055
Ericson M, Löf E, Stomberg R, Chau P, Söderpalm B (2008) Nicotinic acetylcholine receptors in the anterior, but not posterior, ventral tegmental area mediate ethanol-induced elevation of accumbal dopamine levels. J Pharmacol Exp Ther 326(1):76–82
Ericson M, Löf E, Stomberg R, Söderpalm B (2009) The smoking cessation medication varenicline attenuates alcohol and nicotine interactions on the rat mesolimbic dopamine system. J Pharmacol Exp Ther 329(1):225–230
Ericson M, Molander A, Löf E, Engel JA, Söderpalm B (2003) Ethanol elevates accumbal dopamine levels via indirect activation of ventral tegmental nicotinic acetylcholine receptors. Eur J Pharmacol 467(1–3):85–93
Ericson M, Molander A, Stomberg R, Söderpalm B (2006) Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. Eur J Neurosci 23(12):3225–3229
Fahlke C, Hansen S, Engel JA, Hård E (1994) Effects of ventral striatal 6-OHDA lesions or amphetamine sensitization on ethanol consumption in the rat. Pharmacol Biochem Behav 47:345–349
Ferraro L, Tanganelli S, O’Connor WT, Antonelli T, Rambert F, Fuxe K (1996) The vigilance promoting drug modafinil increases dopamine release in the rat nucleus accumbens via the involvement of a local GABAergic mechanism. Eur J Pharmacol 306(1–3):33–39
Floresco SB, Yang CR, Phillips AG, Blaha CD (1998) Basolateral amygdala stimulation evokes glutamate receptor-dependent dopamine efflux in the nucleus accumbens of the anaesthetized rat. Eur J Neurosci 10(4):1241–1251
Foddai M, Dosia G, Spiga S, Diana M (2004) Acetaldehyde increases dopaminergic neuronal activity in the VTA. Neuropsychopharmacology 29:530–536
Forman SA, Righi DL, Miller KW (1989) Ethanol increases agonist affinity for nicotinic receptors from Torpedo. Biochim Biophys Acta 987(1):95–103
Frohlich R, Patzelt C, Illes P (1994) Inhibition by ethanol of excitatory amino acid receptors and nicotinic acetylcholine receptors at rat locus coeruleus neurons. Naunyn-Schmied Arch Pharmacol 350:626–631
Fucito LM, Toll BA, Wu R, Romano DM, Tek E, O’Malley SS (2011) A preliminary investigation of varenicline for heavy drinking smokers. Psychopharmacology (Berl) 215(4):655–663
García-Cabezas MA, Martínez-Sánchez P, Sánchez-González MA, Garzón M, Cavada C (2009) Dopamine innervation in the thalamus: monkey versus rat. Cereb Cortex 19:424–234
George SR, Fan T, Ng GY, Jung SY, O’Dowd BF, Naranjo CA (1995) Low endogenous dopamine function in brain predisposes to high alcohol preference and consumption: reversal by increasing synaptic dopamine. J Pharmacol Exp Ther 273:373–379
Gianoulakis C (1996) Implications of endogenous opioids and dopamine in alcoholism: human and basic science studies. Alcohol Alcohol 31(Suppl 1):33–42
Gianoulakis C, Krishnan B, Thavundayil J (1996) Enhanced sensitivity of pituitary beta-endorphin to ethanol in subjects at high risk of alcoholism. Arch Gen Psychiatry 53(3):250–257
Gonzales RA, Weiss F (1998) Suppression of ethanol-reinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens. J Neurosci 18(24):10663–10671
Grant KA (1994) Emerging neurochemical concepts in the actions of ethanol at ligand-gated ion channels. Behav Pharmacol 5(4–5):383–404
Grudzinska J, Schemm R, Haeger S, Nicke A, Schmalzing G, Betz H, Laube B (2005) The beta subunit determines the ligand binding properties of synaptic glycine receptors. Neuron 45(5):727–739
Guan XM, Yu H, Palyha OC, McKee KK, Feighner SD, Sirinathsinghji DJ, Smith RG, Van der Ploeg LH, Howard AD (1997) Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res 48(1):23–29
Hansen S, Fahlke C, Hård E, Thomasson R (1995) Effects of ibotenic acid lesions of the ventral striatum and the medial prefrontal cortex on ethanol consumption in the rat. Alcohol 12:397–402
Harris BR, Prendergast MA, Gibson DA, Rogers DT, Blanchard JA, Holley RC, Fu MC, Hart SR, Pedigo NW, Littleton JM (2002) Acamprosate inhibits the binding and neurotoxic effects of trans-ACPD, suggesting a novel site of action at metabotropic glutamate receptors. Alcohol Clin Exp Res 26(12):1779–1793
Hedlund L, Wahlström G (1998a) The effect of diazepam on voluntary ethanol intake in a rat model of alcoholism. Alcohol Alcohol 33(3):207–219
Hedlund L, Wahlström G (1998b) Citalopram as an inhibitor of voluntary ethanol intake in the male rat. Alcohol 16(4):295–303
Heinz A, Siessmeier T, Wrase J, Buchholz HG, Grunder G, Kumakura Y, Cumming P, Schreckenberger M, Smolka MN, Rösch F, Mann K, Bartenstein P (2005) Correlation of alcohol craving with striatal dopamine synthesis capacity and D2/3 receptor availability: a combined [18F]DOPA and [18F]DMFP PET study in detoxified alcoholic patients. Am J Psychiatry 162:1515–1520
Hevers W, Lüddens H (1998) The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes. Mol Neurobiol 18:35–86
Hodge CW, Samson HH, Chappelle AM (1997) Alcohol self-administration: further examination of the role of dopamine receptors in the nucleus accumbens. Alcohol Clin Exp Res 21:1083–1091
Hoffman PL, Rabe CS, Moses F, Tabakoff B (1989) N-methyl-D-aspartate receptors and ethanol: inhibition of calcium flux and cyclic GMP production. J Neurochem 52:1937–1940
Howland JG, Taepavarapruk P, Phillips AG (2002) Glutamate receptor-dependent modulation of dopamine efflux in the nucleus accumbens by basolateral, but not central, nucleus of the amygdala in rats. J Neurosci 22(3):1137–1145
Hyytiä P (1993) Involvement of mu-opioid receptors in alcohol drinking by alcohol-preferring AA rats. Pharmacol Biochem Behav 45(3):697–701
Ikemoto S, McBride WJ, Murphy JM, Lumeng L, Li TK (1997) 6-OHDA-lesions of the nucleus accumbens disrupt the acquisition but not the maintenance of ethanol consumption in the alcohol-preferring P line of rats. Alcohol Clin Exp Res 21:1042–1046
Imperato A, Mulas A, Di Chiara G (1986) Nicotine preferentially stimulates dopamine release in the limbic system of freely moving rats. Eur J Pharmacol 132(2–3):337–338
Inoue F, Frank GB (1967) Effects of ethyl alcohol on excitability and on neuromuscular transmission in frog skeletal muscle. Br J Pharmacol 30:186–193
Iorio KR, Reinlib L, Tabakoff B, Hoffman PL (1992) Chronic exposure of cerebellar granule cells to ethanol results in increased N-methyl-D-aspartate receptor function. Mol Pharmacol 41:1142–1148
Jensen AA, Frolund B, Liljefors T, Krogsgaard-Larsen P (2005) Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications and therapeutic inspirations. J Med Chem 48(15):4705–4745
Jerlhag E, Egecioglu E, Dickson SL, Andersson M, Svensson L, Engel JA (2006a) Ghrelin stimulates locomotor activity and accumbal dopamine-overflow via central cholinergic systems in mice: implications for its involvement in brain reward. Addict Biol 11(1):45–54
Jerlhag E, Grøtli M, Luthman K, Svensson L, Engel JA (2006b) Role of the subunit composition of central nicotinic acetylcholine receptors for the stimulatory and dopamine-enhancing effects of ethanol. Alcohol Alcohol 41(5):486–493
Jerlhag E, Egecioglu E, Dickson SL, Douhan A, Svensson L, Engel JA (2007) Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens. Addict Biol 12(1):6–16
Jerlhag E, Egecioglu E, Dickson SL, Svensson L, Engel JA (2008) Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens. Eur Neuropsychopharmacol 18(7):508–518
Jerlhag E, Egecioglu E, Landgren S, Salomé N, Heilig M, Moechars D, Datta R, Perrissoud D, Dickson SL, Engel JA (2009) Requirement of central ghrelin signaling for alcohol reward. Proc Natl Acad Sci U S A 106(27):11318–11323
Jiang LH, Ashby CR Jr, Kasser RJ, Wang RY (1990) The effect of intraventricular administration of the 5-HT3 receptor agonist 2-methylserotonin on the release of dopamine in the nucleus accumbens: an in vivo chronocoulometric study. Brain Res 513:156–160
Jonsson S, Kerekes N, Hyytiä P, Ericson M, Söderpalm B (2009) Glycine receptor expression in the forebrain of male AA/ANA rats. Brain Res 1305(Supplement 1):S27–S36
Kaczmarek HJ, Kiefer SW (2000) Microinjections of dopaminergic agents in the nucleus accumbens affect ethanol consumption but not palatability. Pharmacol Biochem Behav 66:307–312
Kandel ER, Schwartz JH, Jessell TM (2000) Principles of neural science, 4th edn. McGraw-Hill, New York. ISBN 0-8385-7701-6
Karreman M, Moghaddam B (1996) The prefrontal cortex regulates the basal release of dopamine in the limbic striatum: an effect mediated by ventral tegmental area. J Neurochem 66(2):589–598
Karreman M, Westerink BH, Moghaddam B (1996) Excitatory amino acid receptors in the ventral tegmental area regulate dopamine release in the ventral striatum. J Neurochem 67(2):601–607
Karamanakos PN, Pappas P, Stephanou P, Marselos M (2001) Differentiation of disulfiram effects on central catecholamines and hepatic ethanol metabolism. Pharmacol Toxicol 88:106–110
Katner SN, Kerr TM, Weiss F (1996) Ethanol anticipation enhances dopamine efflux in the nucleus accumbens of alcohol-preferring (P) but not Wistar rats. Behav Pharmacol 7(7):669–674
Katner SN, Weiss F (1999) Ethanol-associated olfactory stimuli reinstate ethanol-seeking behavior after extinction and modify extracellular dopamine levels in the nucleus accumbens. Alcohol Clin Exp Res 23(11):1751–1760
Kaur S, Ryabinin AE (2010) Ghrelin receptor antagonism decreases alcohol consumption and activation of perioculomotor urocortin-containing neurons. Alcohol Clin Exp Res 34(9):1525–1534
Kiianmaa K, Andersson K, Fuxe K (1979) On the role of ascending dopamine systems in the control of voluntary ethanol intake and ethanol intoxication. Pharmacol Biochem Behav 10(4):603–608
Kim AK, Souza-Formigoni ML (2010) Disulfiram impairs the development of behavioural sensitization to the stimulant effect of ethanol. Behav Brain Res 207(2):441–446. Epub 2009 Nov 3
Kim DJ, Yoon SJ, Choi B, Kim TS, Woo YS, Kim W, Myrick H, Peterson BS, Choi YB, Kim YK, Jeong J (2005) Increased fasting plasma ghrelin levels during alcohol abstinence. Alcohol Alcohol 40(1):76–79
Kirsch J (2006) Glycinergic transmission. Cell Tissue Res 326(2):535–540
Koistinen M, Tuomainen P, Hyytiä P, Kiianmaa K (2001) Naltrexone suppresses ethanol intake in 6-hydroxydopamine-treated rats. Alcohol Clin Exp Res 25:1605–1612
Koob GF (1992) Neural mechanisms of drug reinforcement. The neurobiology of drug and alcohol addiction, vol 654, PW Kalivas and HH Samson. New York. pp 171–191
Koob GF, LeMoal M (2001) Drug Addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24:97–129
Korpi ER (1994) Role of GABAA receptors in the actions of alcohol and in alcoholism: recent advances. Alcohol Alcohol 29:115–129
Kraus T, Schanze A, Gröschl M, Bayerlein K, Hillemacher T, Reulbach U, Kornhuber J, Bleich S (2005) Ghrelin levels are increased in alcoholism. Alcohol Clin Exp Res 29(12):2154–2157
Kuhse J, Betz H, Kirsch J (1995) The inhibitory glycine receptor: architecture, synaptic localization and molecular pathology of a postsynaptic ion-channel complex. Curr Opin Neurobiol 5(3):318–323
Landgren S, Simms JA, Hyytiä P, Engel JA, Bartlett SE, Jerlhag E (2011) Ghrelin receptor (GHS-R1A) antagonism suppresses both operant alcohol self-administration and high alcohol consumption in rats. Addict Biol. doi: 10.1111/j.1369-1600.2010.00280.x
Larsson A, Edström L, Svensson L, Söderpalm B, Engel JA (2005) Voluntary ethanol intake increases extracellular acetylcholine levels in the ventral tegmental area in the rat. Alcohol Alcohol 40(5):349–358
Larsson A, Jerlhag E, Svensson L, Söderpalm B, Engel JA (2004) Is an alpha-conotoxin MII-sensitive mechanism involved in the neurochemical, stimulatory, and rewarding effects of ethanol? Alcohol 34(2–3):239–250
Le AD, Corrigall WA, Harding JW, Juzytsch W, Li TK (2000) Involvement of nicotinic receptors in alcohol self-administration. Alcohol Clin Exp Res 24(2):155–163
Levy AD, Murphy JM, McBride WJ, Lumeng L, Li TK (1991) Microinjection of sulpiride into the nucleus accumbens increases ethanol drinking in alcohol-preferring (P) rats. Alcohol Alcohol Suppl 1:417–420
Li Y, Xu TL (2002) State-dependent cross-inhibition between anionic GABA(A) and glycine ionotropic receptors in rat hippocampal CA1 neurons. Neuroreport 13:223–226
Li Z, Zharikova A, Bastian J, Esperon L, Hebert N, Mathes C, Rowland NE, Peris J (2008) High temporal resolution of amino acid levels in rat nucleus accumbens during operant ethanol self-administration: involvement of elevated glycine in anticipation. J Neurochem 106(1):170–181
Lidö HH, Stomberg R, Fagerberg A, Ericson M, Söderpalm B (2009) Glycine reuptake inhibition: a novel principle for prevention of ethanol-induced dopamine release. Alcohol Clin Exp Res 33(7):1–7
Lisman JE, Pi HJ, Zhang Y, Otmakhova NA (2010) A thalamo-hippocampal-ventral tegmental area loop may produce the positive feedback that underlies the psychotic break in schizophrenia. Biol Psychiatry 68(1):17–24
Liu W, Thielen RJ, Rodd ZA, McBride WJ (2006) Activation of serotonin-3 receptors increases dopamine release within the ventral tegmental area of Wistar and alcohol-preferring (P) rats. Alcohol 40:167–176
Löf E, Ericson M, Stomberg R, Söderpalm B (2007a) Characterization of ethanol-induced dopamine elevation in the rat nucleus accumbens. Eur J Pharmacol 555(2–3):148–155
Löf E, Olausson P, deBejczy A, Stomberg R, McIntosh JM, Taylor JR, Söderpalm B (2007b) Nicotinic acetylcholine receptors in the ventral tegmental area mediate the dopamine activating and reinforcing properties of ethanol cues. Psychopharmacology (Berl) 195(3):333–343
Lopreato GF, Banerjee P, Mihic SJ (2003) Amino acids in transmembrane domain two influence anesthetic enhancement of serotonin-3A receptor function. Brain Res Mol Brain Res 118:45–51
Lovinger DM (1991) Ethanol potentiates ion current mediated by 5-HT3 receptors on neuroblastoma cells and isolated neurons. Alcohol Alcohol Suppl 1:181–185
Lovinger DM, White G, Weight FF (1989) Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243:1721–1724
Lovinger DM, White G (1991) Ethanol potentiation of 5-hydroxytryptamine3 receptor-mediated ion current in neuroblastoma cells, isolated adult mammalian neurons. Mol Pharmacol 40:263–270
Lovinger DM, Zhou Q (1998) Alcohol effects on the 5-HT3 ligand-gated ion channel. Toxicol Lett 100–101:239–246
Lüddens H, Korpi ER (1995) Biological function of GABAA/benzodiazepine receptor heterogeneity. J Psychiatr Res 29:77–94
Lukas RJ, Changeux JP, Le Novère N, Albuquerque EX, Balfour DJ, Berg DK, Bertrand D, Chiappinelli VA, Clarke PB, Collins AC, Dani JA, Grady SR, Kellar KJ, Lindstrom JM, Marks MJ, Quik M, Taylor PW, Wonnacott S (1999) International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits. Pharmacol Rev 51(2):397–401
Lynch JW (2004) Molecular structure and function of the glycine receptor chloride channel. Physiol Rev 84(4):1051–1095
Lyness WH, Smith FL (1992) Influence of dopaminergic and serotonergic neurons on intravenous ethanol self-administration in the rat. Pharmacol Biochem Behav 42:187–192
Malosio ML, Marqueze-Pouey B, Kuhse J, Betz H (1991) Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. Embo J 10:2401–2409
Mansour A, Fox CA, Akil H, Watson SJ (1995) Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications. Trends Neurosci 18(1):22–29
Martinez D, Gil R, Slifstein M, Hwang DR, Huang Y, Perez A, Kegeles L, Talbot P, Evans S, Krystal J, Laruelle M, Abi-Dargham A (2005) Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biol Psychiatry 58:779–786
Marzalec W, Aistrup GL, Narahashi T (1999) Ethanol-nicotine interactions at alpha-bungarotoxin-insensitive nicotinic acetylcholine receptors in rat cortical neurons. Alcohol Clin Exp Res 23:439–445
Mascia MP, Maiya R, Borghese CM, Lobo IA, Hara K, Yamakura T, Gong DH, Beckstead MJ (2001) Does acetaldehyde mediate ethanol action in the central nervous system? Alcohol Clin Exp Res 25:1570–1575
Mascia MP, Mihic SJ, Valenzuela CF, Schofield PR, Harris RA (1996) A single amino acid determines differences in ethanol actions on strychnine-sensitive glycine receptors. Mol Pharmacol 50(2):402–406
McKee SA, Harrison EL, O’Malley SS, Krishnan-Sarin S, Shi J, Tetrault JM, Picciotto MR, Petrakis IL, Estevez N, Balchunas E (2009) Varenicline reduces alcohol self-administration in heavy-drinking smokers. Biol Psychiatry 66:185–190
Mehta AK, Ticku MK (1988) Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves gamma-aminobutyric acidA-gated chloride channels. J Pharmacol Exp Ther 246:558–564
Mehta AK, Ticku MK (1999) An update on GABAA receptors. Brain Res Brain Res Rev 29:196–217
Melendez RI, Rodd-Henricks ZA, Engleman EA, Li TK, McBride WJ, Murphy JM (2002) Microdialysis of dopamine in the nucleus accumbens of alcohol-preferring (P) rats during anticipation and operant self-administration of ethanol. Alcohol Clin Exp Res 26(3):318–325
Melis M, Enrico P, Peana AT, Diana M (2007) Acetaldehyde mediates alcohol activation of the mesolimbic dopamine system. Eur J Neurosci 26:2824–2833
Mhatre MC, Ticku MK (1993) Alcohol: effects on GABAA receptor function and gene expression. Alcohol Alcohol Suppl 2:331–335
Michel ME, Bolger G, Weissman BA (1985) Binding of a new opiate antagonist, nalmefene, to rat brain membranes. Methods Find Exp Clin Pharmacol 7(4):175–177
Moghaddam B, Gruen RJ, Roth RH, Bunney BS, Adams RN (1990) Effect of L-glutamate on the release of striatal dopamine: in vivo dialysis and electrochemical studies. Brain Res 518(1-2):55–60
Moghaddam B, Bolinao ML (1994) Biphasic effect of ethanol on extracellular accumulation of glutamate in the hippocampus and the nucleus accumbens. Neurosci Lett 178(1):99–102
Molander A, Söderpalm B (2005a) Glycine receptors regulate dopamine release in the rat nucleus accumbens. Alcohol Clin Exp Res 29:17–26
Molander A, Söderpalm B (2005b) Accumbal strychnine-sensitive glycine receptors: an access point for ethanol to the brain reward system. Alcohol Clin Exp Res 29:27–37
Molander A, Lidö HH, Löf E, Ericson M, Söderpalm B (2007) The glycine reuptake inhibitor Org 25935 decreases ethanol intake and preference in male wistar rats. Alcohol Alcohol 42(1):11–18
Molander A, Löf E, Stomberg R, Ericson M, Söderpalm B (2005) Involvement of accumbal glycine receptors in the regulation of voluntary ethanol intake in the rat. Alcohol Clin Exp Res 29:38–45
Myers WD, Ng KT, Singer G (1982) Intravenous self-administration of acetaldehyde in the rat as a function of schedule, food deprivation and photoperiod. Pharmacol Biochem Behav 17:807–811
Nealey KA, Smith AW, Davis SM, Smith DG, Walker BM (2011) κ-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats. Neuropharmacology 61(1–2):35–42
Nordberg A, Wahlstrom G, Eriksson B (1985) Relations between muscimol, quinuclidinyl benzilate and nicotine binding sites in brain after very long treatment with ethanol in rats. Eur J Pharmacol 115(2–3):301–304
Okada K (1967) Effects of alcohols and acetone on the neuromuscular junction of frog. Jpn J Physiol 17:412–413
Olausson P, Jentsch JD, Taylor JR (2004a) Nicotine enhances responding with conditioned reinforcement. Psychopharmacology (Berl) 171:173–178
Olausson P, Jentsch JD, Taylor JR (2004b) Repeated nicotine exposure enhances responding with conditioned reinforcement. Psychopharmacology (Berl) 173:98–104
Olive MF, Nannini MA, Ou CJ, Koenig HN, Hodge CW (2002) Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release. Eur J Pharmacol 437(1–2):55–61
Olsen RW, Hanchar HJ, Meera P, Wallner M (2007) GABAA receptor subtypes: the “one glass of wine” receptors. Alcohol 41:201–209
Ortiz A, Griffiths PJ, Littleton JM (1974) A comparison of the effects of chronic administration of ethanol and acetaldehyde to mice: evidence for a role of acetaldehyde in ethanol dependence. J Pharm Pharmacol 26:249–260
Oslin DW, Berrettini W, Kranzler HR, Pettinati H, Gelernter J, Volpicelli JR, O’Brien CP (2003) A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 28:1546–1552
Parsons LH, Justice JB Jr (1993) Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis. Brain Res 606:195–199
Penland S, Hoplight B, Obernier J, Crews FT (2001) Effects of nicotine on ethanol dependence and brain damage. Alcohol 24(1):45–54
Peoples RW, White G, Lovinger DM, Weight FF (1997) Ethanol inhibition of N-methyl-D-aspartate-activated current in mouse hippocampal neurones: whole-cell patch-clamp analysis. Br J Pharmacol 122:1035–1042
Pettit HO, Ettenberg A, Bloom FE, Koob GF (1984) Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psychopharmacology (Berl) 84(2):167–173
Petrakis I, Ralevski E, OBrien E, Jane S, Keegan K, Rounsaville B, Krystal J (2008) Mecamylamine treatment for alcohol dependence in smokers and non-smokers. Alcohol Clin Exp Ther Suppl 32(6):256A
Phillips TJ, Brown KJ, Burkhart-Kasch S, Wenger CD, Kelly MA, Rubinstein M, Grandy DK, Low MJ (1998) Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D2 receptors. Nat Neurosci 1:610–615
Popp RL, Lickteig R, Browning MD, Lovinger DM (1998) Ethanol sensitivity and subunit composition of NMDA receptors in cultured striatal neurons. Neuropharmacology 37:45–56
Quarfordt SD, Kalmus GW, Myers RD (1991) Ethanol drinking following 6-OHDA lesions of nucleus accumbens and tuberculum olfactorium of the rat. Alcohol 8:211–217
Quertemont E, Tambour S, Tirelli E (2005) The role of acetaldehyde in the neurobehavioral effects of ethanol: a comprehensive review of animal studies. Prog Neurobiol 75(4):247–274
Rabe CS, Tabakoff B (1990) Glycine site-directed agonists reverse the actions of ethanol at the N-methyl-D-aspartate receptor. Mol Pharmacol 38:753–757
Racca C, Gardiol A, Triller A (1998) Cell-specific dendritic localization of glycine receptor alpha subunit messenger RNAs. Neuroscience 84(4):997–1012
Rajendra S, Lynch JW, Schofield PR (1997) The glycine receptor. Pharmacol Ther 73(2):121–146
Ramchandani VA, Umhau J, Pavon FJ, Ruiz-Velasco V, Margas W, Sun H, Damadzic R, Eskay R, Schoor M, Thorsell A, Schwandt ML, Sommer WH, George DT, Parsons LH, Herscovitch P, Hommer D, Heilig M (2011) A genetic determinant of the striatal dopamine response to alcohol in men. Mol Psychiatry 16:809–817
Rassnick S, Pulvirenti L, Koob GF (1992) Oral ethanol self-administration in rats is reduced by the administration of dopamine and glutamate receptor antagonists into the nucleus accumbens. Psychopharmacology (Berl) 109:92–98
Rassnick S, Stinus L, Koob GF (1993) The effects of 6-hydroxydopamine lesions of the nucleus accumbens and the mesolimbic dopamine system on oral self-administration of ethanol in the rat. Brain Res 623:16–24
Ray LA, Hutchison KE (2007) Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled study. Arch Gen Psychiatry 64(9):1069–1077
Reid MS, Mickalian JD, Delucchi KL, Berger SP (1999) A nicotine antagonist, mecamylamine, reduces cue-induced cocaine craving in cocaine-dependent subjects. Neuropsychopharmacology 20:297–307
Reid MS, Mickalian JD, Delucchi KL, Hall SM, Berger SP (1998) An acute dose of nicotine enhances cue-induced cocaine craving. Drug Alcohol Depend 49:95–104
Rezvani AH, Levin ED (2002) Nicotine-alcohol interactions and cognitive function in rats. Pharmacol Biochem Behav 72(4):865–872
Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18(3):247–291
Rodd ZA, Bell RL, Oster SM, Toalston JE, Pommer TJ, McBride WJ, Murphy JM (2010) Serotonin-3 receptors in the posterior ventral tegmental area regulate ethanol self-administration of alcohol-preferring (P) rats. Alcohol 44:245–255
Rodd ZA, Bell RL, Zhang Y, Murphy JM, Goldstein A, Zaffaroni A, Li TK, McBride WJ (2005) Regional heterogeneity for the intracranial self-administration of ethanol and acetaldehyde within the ventral tegmental area of alcohol-preferring (P) rats: involvement of dopamine and serotonin. Neuropsychopharmacology 30:330–338
Rodd ZA, Gryszowka VE, Toalston JE, Oster SM, Ji D, Bell RL, McBride WJ (2007) The reinforcing actions of a serotonin-3 receptor agonist within the ventral tegmental area: evidence for subregional and genetic differences and involvement of dopamine neurons. J Pharmacol Exp Ther 321:1003–1012
Rodd-Hendricks ZA, Melendez RI, Zaffaroni A, Goldstein A, McBride WJ, Li TK (2002) The reinforcing effects of acetaldehyde in the posterior ventral tegmental area of alcohol-preferring rats. Pharmacol Biochem Behav 72:55–64
Rüsch D, Musset B, Wulf H, Schuster A, Raines DE (2007) Subunit-dependent modulation of the 5-hydroxytryptamine type 3 receptor open-close equilibrium by n-alcohols. J Pharmacol Exp Ther 321:1069–1074
Sánchez-González MA, García-Cabezas MA, Rico B, Cavada C (2005) The primate thalamus is a key target for brain dopamine. J Neurosci 25:6076–6083
Santhakumar V, Wallner M, Otis TS (2007) Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition. Alcohol 41:211–221
Sato K, Zhang JH, Saika T, Sato M, Tada K, Tohyama M (1991) Localization of glycine receptor alpha 1 subunit mRNA-containing neurons in the rat brain: an analysis using in situ hybridization histochemistry. Neuroscience 43(2–3):381–395
Sato K, Kiyama H, Tohyama M (1992) Regional distribution of cells expressing glycine receptor alpha 2 subunit mRNA in the rat brain. Brain Res 590(1–2):95–108
Schilström B, Fagerquist MV, Zhang X, Hertel P, Panagis G, Nomikos GG, Svensson TH (2000) Putative role of presynaptic alpha7* nicotinic receptors in nicotine stimulated increases of extracellular levels of glutamate and aspartate in the ventral tegmental area. Synapse 38(4):375–383
Schilström B, Rawal N, Mameli-Engvall M, Nomikos GG, Svensson TH (2003) Dual effects of nicotine on dopamine neurons mediated by different nicotinic receptor subtypes. Int J Neuropsychopharmacol 6(1):1–11
Schneider ER, Rada P, Darby RD, Leibowitz SF, Hoebel BG (2007) Orexigenic peptides and alcohol intake: differential effects of orexin, galanin, and ghrelin. Alcohol Clin Exp Res 31(11):1858–1865
Schulteis G, Markou A, Cole M, Koob GF (1995) Decreased brain reward produced by ethanol withdrawal. Proc Natl Acad Sci USA 92(13):5880–5884
Schulz R, Wüster M, Duka T, Herz A (1980) Acute and chronic ethanol treatment changes endorphin levels in brain and pituitary. Psychopharmacology (Berl) 68(3):221–227
Seizinger BR, Bovermann K, Maysinger D, Höllt V, Herz A (1983) Differential effects of acute and chronic ethanol treatment on particular opioid peptide systems in discrete regions of rat brain and pituitary. Pharmacol Biochem Behav 18 Suppl 1:361–369
Shoemaker WJ, Vavrousek-Jakuba E, Arons CD, Kwok FC (2002) The acquisition and maintenance of voluntary ethanol drinking in the rat: effects of dopaminergic lesions and naloxone. Behav Brain Res 137:139–148
Smith BR, Amit Z, Splawinsky J (1984) Conditioned place preference induced by intraventricular infusions of acetaldehyde. Alcohol 1:193–195
Snell LD, Nunley KR, Lickteig RL, Browning MD, Tabakoff B, Hoffman PL (1996) Regional and subunit specific changes in NMDA receptor mRNA and immunoreactivity in mouse brain following chronic ethanol ingestion. Brain Res Mol Brain Res 40:71–78
Snell LD, Tabakoff B, Hoffman PL (1993) Radioligand binding to the N-methyl-D-aspartate receptor/ionophore complex: alterations by ethanol in vitro and by chronic in vivo ethanol ingestion. Brain Res 602:91–98
Söderpalm B, Ericson M, Olausson P, Blomqvist O, Engel JA (2000) Nicotinic mechanisms involved in the dopamine activating and reinforcing properties of ethanol. Behav Brain Res 113:85–96
Söderpalm B, Löf E, Ericson M (2009) Mechanistic studies of ethanol’s interaction with the mesolimbic dopamine reward system. Pharmacopsychiatry 42(Suppl 1):S87–S94
Song W, Chattipakorn SC, McMahon LL (2006) Glycine-gated chloride channels depress synaptic transmission in rat hippocampus. J Neurophysiol 95(4):2366–2379
Spanagel R, Weiss F (1999) The dopamine hypothesis of reward: past and current status. Trends Neurosci 22(11):521–527
Steensland P, Simms JA, Holgate J, Richards JK, Bartlett SE (2007) Varenicline, an {alpha}4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking. PNAS 104(30):12518–12523
Suzdak PD, Schwartz RD, Skolnick P, Paul SM (1986) Ethanol stimulates gamma-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes. Proc Natl Acad Sci U S A 83:4071–4075
Tan KR, Brown M, Labouèbe G, Yvon C, Creton C, Fritschy JM, Rudolph U, Lüscher C (2010) Neural bases for addictive properties of benzodiazepines. Nature 463:769–774
Tanganelli S, O’Connor WT, Ferraro L, Bianchi C, Beani L, Ungerstedt U, Fuxe K (1994) Facilitation of GABA release by neurotensin is associated with a reduction of dopamine release in rat nucleus accumbens. Neuroscience 60(3):649–657
Ticku MK (1990) Alcohol and GABA-benzodiazepine receptor function. Ann Med 22:241–246
Ticku MK, Lowrimore P, Lehoullier P (1986) Ethanol enhances GABA-induced 36Cl-influx in primary spinal cord cultured neurons. Brain Res Bull 17:123–126
Tizabi Y, Bai L, Copeland RL Jr, Taylor RE (2007) Combined effects of systemic alcohol and nicotine on dopamine release in the nucleus accumbens shell. Alcohol Alcohol 42(5):413–416
Tizabi Y, Copeland RL Jr, Louis VA, Taylor RE (2002) Effects of combined systemic alcohol and central nicotine administration into ventral tegmental area on dopamine release in the nucleus accumbens. Alcohol Clin Exp Res 26(3):394–399
Trigo JM, Martin-García E, Berrendero F, Robledo P, Maldonado R (2010) The endogenous opioid system: a common substrate in drug addiction. Drug Alcohol Depend 108(3):183–194
Urban NB, Kegeles LS, Slifstein M, Xu X, Martinez D, Sakr E, Castillo F, Moadel T, O’Malley SS, Krystal JH, Abi-Dargham A (2010) Sex differences in striatal dopamine release in young adults after oral alcohol challenge: a positron emission tomography imaging study with [¹¹C]raclopride. Biol Psychiatry 68:689–696
Vengeliene V, Leonardi-Essmann F, Sommer WH, Marston HM, Spanagel R (2010) Glycine transporter-1 blockade leads to persistently reduced relapse-like alcohol drinking in rats. Biol Psychiatry 68(8):704–711
Volkow ND, Wang GJ, Fowler JS, Logan J, Hitzemann R, Ding YS, Pappas N, Shea C, Piscani K (1996) Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin Exp Res 20:1594–1598
Volkow ND, Wang GJ, Maynard L, Fowler JS, Jayne B, Telang F, Logan J, Ding YS, Gatley SJ, Hitzemann R, Wong C, Pappas N (2002) Effects of alcohol detoxification on dopamine D2 receptors in alcoholics: a preliminary study. Psychiatry Res 116:163–172
Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Jayne M, Ma Y, Pradhan K, Wong C (2007) Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement. J Neurosci 27:12700–12706
Volpicelli JR, Davis MA, Olgin JE (1986) Naltrexone blocks the post-shock increase of ethanol consumption. Life Sci 38(9):841–847
Wallner M, Olsen RW (2008) Physiology and pharmacology of alcohol: the imidazobenzodiazepine alcohol antagonist site on subtypes of GABAA receptors as an opportunity for drug development? Br J Pharmacol 154:288–298
Walker BM, Koob GF (2008) Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence. Neuropsychopharmacology 33(3):643–652
Weiss F, Lorang MT, Bloom FE, Koob GF (1993) Oral alcohol self-administration stimulates dopamine release in the rat nucleus accumbens: genetic and motivational determinants. J Pharmacol Exp Ther 267:250–258
Weiss F, Parsons LH, Schulteis G, Hyytiä P, Lorang MT, Bloom FE, Koob GF (1996) Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci 16(10):3474–3485
Wise RA (1987) The role of reward pathways in the development of drug dependence. Pharmacol Ther 35(1–2):227–263
Wise RA, Rompre PP (1989) Brain dopamine and reward. Annu Rev Psychol 40:191–225
Wozniak KM, Pert A, Linnoila M (1990) Antagonism of 5-HT3 receptors attenuates the effects of ethanol on extracellular dopamine. Eur J Pharmacol 187:287–289
Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR (2000) The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 141(11):4325–4328
Wu G, Miller KW (1994) Ethanol enhances agonist-induced fast desensitization in nicotinic acetylcholine receptors. Biochemistry 33(31):9085–9091
Xiao C, Shao XM, Olive MF, Griffin WC 3rd, Li KY, Krnjevic K, Zhou C, Ye JH (2009) Ethanol facilitates glutamatergic transmission to dopamine neurons in the ventral tegmental area. Neuropsychopharmacology 34(2):307–318
Xiao C, Zhang J, Krnjevic K, Ye JH (2007) Effects of ethanol on midbrain neurons: role of opioid receptors. Alcohol Clin Exp Res 31(7):1106–1113
Xiao C, Ye JH (2008) Ethanol dually modulates GABAergic synaptic transmission onto dopaminergic neurons in ventral tegmental area: role of mu-opioid receptors. Neuroscience 153(1):240–248
Yang X, Criswell HE, Breese GR (1999a) Action of ethanol on responses to nicotine from cerebellar interneurons and medial septal neurons: relationship to methyllycaconitine inhibition of nicotine responses. Alcohol Clin Exp Res 23:983–990
Yang X, Criswell HE, Breese GR (1999b) Action of ethanol on responses to nicotine from cerebellar Purkinje neurons: relationship to methyllycaconitine (MLA) inhibition of nicotine responses. Neurochem Int 35:185–194
Yao L, Fan P, Arolfo M, Jiang Z, Olive MF, Zablocki J, Sun HL, Chu N, Lee J, Kim HY, Leung K, Shryrock J, Blackburn B, Diamond I (2010) Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use-dependent inhibitor of dopamine synthesis. Nat Med 16:1024–1028
Ye J (2000) Physiology and pharmacology of native glycine receptors in developing rat ventral tegmental area neurons. Brain Res 862(1–2):74–82
Yoder KK, Constantinescu CC, Kareken DA, Normandin MD, Cheng TE, O’Connor SJ, Morris ED (2007) Heterogeneous effects of alcohol on dopamine release in the striatum: a PET study. Alcohol Clin Exp Res 31:965–973
Yoshida K, Engel J, Liljequist S (1982) The effect of chronic ethanol administration of high affinity 3H-nicotinic binding in rat brain. Naunyn Schmiedebergs Arch Pharmacol 321(1):74–76
Yoshimoto K, McBride WJ, Lumeng L, Li TK (1992) Alcohol stimulates the release of dopamine and serotonin in the nucleus accumbens. Alcohol 9:17–22
Yoshimoto K, Yayama K, Sorimachi Y, Tani J, Ogata M, Nishimura A, Yoshida T, Ueda S, Komura S (1996) Possibility of 5-HT3 receptor involvement in alcohol dependence: a microdialysis study of nucleus accumbens dopamine and serotonin release in rats with chronic alcohol consumption. Alcohol Clin Exp Res 20(9 Suppl):311A–319A
Young EM, Mahler S, Chi H, de Wit H (2005) Mecamylamine and ethanol preference in healthy volunteers. Alcohol Clin Exp Res 29:58–65
Youngren KD, Daly DA, Moghaddam B (1993) Distinct actions of endogenous excitatory amino acids on the outflow of dopamine in the nucleus accumbens. J Pharmacol Exp Ther 264(1):289–293
Yu D, Zhang L, Eiselé JL, Bertrand D, Changeux JP, Weight FF (1996) Ethanol inhibition of nicotinic acetylcholine type alpha 7 receptors involves the amino-terminal domain of the receptor. Mol Pharmacol 50(4):1010–1016
Zachariou V, Caldarone BJ, Weathers-Lowin A, George TP, Elsworth JD, Roth RH, Changeux JP, Picciotto MR (2001) Nicotine receptor inactivation decreases sensitivity to cocaine. Neuropsychopharmacology 24:576–589
Zeise ML, Kasparov S, Capogna M, Zieglgänsberger W (1993) Acamprosate (calciumacetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors. Eur J Pharmacol 231(1):47–52
Zetterström T, Fillenz M (1990) Local administration of flurazepam has different effects on dopamine release in striatum and nucleus accumbens: a microdialysis study. Neuropharmacology 29(2):129–134
Zhang HX, Thio LL (2007) Zinc enhances the inhibitory effects of strychnine-sensitive glycine receptors in mouse hippocampal neurons. J Neurophysiol 98(6):3666–3676
Zhang L, Hosoi M, Fukuzawa M, Sun H, Rawlings RR, Weight FF (2002) Distinct molecular basis for differential sensitivity of the serotonin type 3A receptor to ethanol in the absence and presence of agonist. J Biol Chem 277:46256–46264
Zhang LH, Gong N, Fei D, Xu L, Xu TL (2008) Glycine uptake regulates hippocampal network activity via glycine receptor-mediated tonic inhibition. Neuropsychopharmacology 33:701–711
Zhang LH, Xu L, Xu TL (2006) Glycine receptor activation regulates short-term plasticity in CA1 area of hippocampal slices of rats. Biochem Biophys Res Commun 344:721–726
Zheng F, Johnson SW (2001) Glycine receptor-mediated inhibition of dopamine and non-dopamine neurons of the rat ventral tegmental area in vitro. Brain Res 919(2):313–317
Zimatkin SM, Pronko SP, Vasiliou V, Gonzalez FJ, Deitrich RA (2006) Enzymatic mechanisms of ethanol oxidation in the brain. Alcohol Clin Exp Res 30:1500–1505
Zuo Y, Aistrup GL, Marszalec W, Gillespie A, Chavez-Noriega LE, Yeh JZ, Narahashi T (2001) Dual action of n-alcohols on neuronal nicotinic acetylcholine receptors. Mol Pharmacol 60(4):700–711
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Söderpalm, B., Ericson, M. (2011). Neurocircuitry Involved in the Development of Alcohol Addiction: The Dopamine System and its Access Points. In: Sommer, W., Spanagel, R. (eds) Behavioral Neurobiology of Alcohol Addiction. Current Topics in Behavioral Neurosciences, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28720-6_170
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