Abstract
Alcohol use disorders are a leading public health concern, engendering enormous costs in terms of both economic loss and human suffering. These disorders are characterized by compulsive and excessive alcohol use, as well as negative affect and alcohol craving during abstinence. Extensive research has implicated the dopamine system in both the acute pharmacological effects of alcohol and the symptomology of alcohol use disorders that develop after extended alcohol use. Preclinical research has shed light on many mechanisms by which chronic alcohol exposure dysregulates the dopamine system. However, many of the findings are inconsistent across experimental parameters such as alcohol exposure length, route of administration, and model organism. We propose that the dopaminergic alterations driving the core symptomology of alcohol use disorders are likely to be relatively stable across experimental settings. Recent work has been aimed at using multiple model organisms (mouse, rat, monkey) across various alcohol exposure procedures to search for commonalities. Here, we review recent advances in our understanding of the effects of chronic alcohol use on the dopamine system by highlighting findings that are consistent across experimental setting and species.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Abrahao KP, Salinas AG, Lovinger DM (2017) Alcohol and the brain: neuronal molecular targets, synapses, and circuits. Neuron 96:1223–1238
Alcantara AA, Chen V, Herring BE, Mendenhall JM, Berlanga ML (2003) Localization of dopamine D2 receptors on cholinergic interneurons of the dorsal striatum and nucleus accumbens of the rat. Brain Res 986:22–29
Allain F, Minogianis EA, Roberts DC, Samaha AN (2015) How fast and how often: the pharmacokinetics of drug use are decisive in addiction. Neurosci Biobehav Rev 56:166–179
Anderson RI, Becker HC (2017) Role of the dynorphin/kappa opioid receptor system in the motivational effects of ethanol. Alcohol Clin Exp Res 41:1402–1418
Anderson RI, Lopez MF, Becker HC (2016a) Forced swim stress increases ethanol consumption in C57BL/6J mice with a history of chronic intermittent ethanol exposure. Psychopharmacology 233:2035–2043
Anderson RI, Lopez MF, Becker HC (2016b) Stress-induced enhancement of ethanol intake in C57BL/6J mice with a history of chronic ethanol exposure: involvement of kappa opioid receptors. Front Cell Neurosci 10:45
Appel SB, Liu Z, McElvain MA, Brodie MS (2003) Ethanol excitation of dopaminergic ventral tegmental area neurons is blocked by quinidine. J Pharmacol Exp Ther 306:437–446
Ariansen JL, Heien ML, Hermans A, Phillips PE, Hernadi I, Bermudez MA, Schultz W, Wightman RM (2012) Monitoring extracellular pH, oxygen, and dopamine during reward delivery in the striatum of primates. Front Behav Neurosci 6:36
Aryal P, Dvir H, Choe S, Slesinger PA (2009) A discrete alcohol pocket involved in GIRK channel activation. Nat Neurosci 12:988–995
Baker EJ, Farro J, Gonzales S, Helms C, Grant KA (2014) Chronic alcohol self-administration in monkeys shows long-term quantity/frequency categorical stability. Alcohol Clin Exp Res 38:2835–2843
Baker EJ, Walter NA, Salo A, Rivas Perea P, Moore S, Gonzales S, Grant KA (2017) Identifying future drinkers: behavioral analysis of monkeys initiating drinking to intoxication is predictive of future drinking classification. Alcohol Clin Exp Res 41:626–636
Bazov I, Kononenko O, Watanabe H, Kuntic V, Sarkisyan D, Taqi MM, Hussain MZ, Nyberg F, Yakovleva T, Bakalkin G (2013) The endogenous opioid system in human alcoholics: molecular adaptations in brain areas involved in cognitive control of addiction. Addict Biol 18:161–169
Belin D, Everitt BJ (2008) Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum. Neuron 57:432–441
Bello EP, Mateo Y, Gelman DM, Noain D, Shin JH, Low MJ, Alvarez VA, Lovinger DM, Rubinstein M (2011) Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors. Nat Neurosci 14:1033–1038
Blaine SK, Sinha R (2017) Alcohol, stress, and glucocorticoids: from risk to dependence and relapse in alcohol use disorders. Neuropharmacology 122:136–147
Bonthius DJ, West JR (1990) Alcohol-induced neuronal loss in developing rats: increased brain damage with binge exposure. Alcohol Clin Exp Res 14:107–118
Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268
Bradberry CW (2002) Dose-dependent effect of ethanol on extracellular dopamine in mesolimbic striatum of awake rhesus monkeys: comparison with cocaine across individuals. Psychopharmacology 165:67–76
Brodie MS (2002) Increased ethanol excitation of dopaminergic neurons of the ventral tegmental area after chronic ethanol treatment. Alcohol Clin Exp Res 26:1024–1030
Brodie MS, Shefner SA, Dunwiddie TV (1990) Ethanol increases the firing rate of dopamine neurons of the rat ventral tegmental area in vitro. Brain Res 508:65–69
Brodie MS, Pesold C, Appel SB (1999) Ethanol directly excites dopaminergic ventral tegmental area reward neurons. Alcohol Clin Exp Res 23:1848–1852
Bruchas MR, Chavkin C (2010) Kinase cascades and ligand-directed signaling at the kappa opioid receptor. Psychopharmacology 210:137–147
Budygin EA, John CE, Mateo Y, Daunais JB, Friedman DP, Grant KA, Jones SR (2003) Chronic ethanol exposure alters presynaptic dopamine function in the striatum of monkeys: a preliminary study. Synapse 50:266–268
Budygin EA, Oleson EB, Mathews TA, Lack AK, Diaz MR, McCool BA, Jones SR (2007) Effects of chronic alcohol exposure on dopamine uptake in rat nucleus accumbens and caudate putamen. Psychopharmacology 193:495–501
Calipari ES, Ferris MJ, Zimmer BA, Roberts DC, Jones SR (2013) Temporal pattern of cocaine intake determines tolerance vs sensitization of cocaine effects at the dopamine transporter. Neuropsychopharmacology 38:2385–2392
Carlezon WA Jr, Chartoff EH (2007) Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation. Nat Protoc 2:2987–2995
Cervera-Juanes R, Wilhem LJ, Park B, Lee R, Locke J, Helms C, Gonzales S, Wand G, Jones SR, Grant KA et al (2016) MAOA expression predicts vulnerability for alcohol use. Mol Psychiatry 21:472–479
Chu B, Dopico AM, Lemos JR, Treistman SN (1998) Ethanol potentiation of calcium-activated potassium channels reconstituted into planar lipid bilayers. Mol Pharmacol 54:397–406
Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, She X, Bult CJ, Agarwala R, Cherry JL, DiCuccio M et al (2009) Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol 7:e1000112
Clarke R, Adermark L (2015) Dopaminergic regulation of striatal interneurons in reward and addiction: focus on alcohol. Neural Plast 2015:814567
Cools R, Frank MJ, Gibbs SE, Miyakawa A, Jagust W, D’Esposito M (2009) Striatal dopamine predicts outcome-specific reversal learning and its sensitivity to dopaminergic drug administration. J Neurosci 29:1538–1543
Cragg SJ, Rice ME (2004) DAncing past the DAT at a DA synapse. Trends Neurosci 27:270–277
Cuzon Carlson VC, Seabold GK, Helms CM, Garg N, Odagiri M, Rau AR, Daunais J, Alvarez VA, Lovinger DM, Grant KA (2011) Synaptic and morphological neuroadaptations in the putamen associated with long-term, relapsing alcohol drinking in primates. Neuropsychopharmacology 36:2513–2528
Danjo T, Yoshimi K, Funabiki K, Yawata S, Nakanishi S (2014) Aversive behavior induced by optogenetic inactivation of ventral tegmental area dopamine neurons is mediated by dopamine D2 receptors in the nucleus accumbens. Proc Natl Acad Sci U S A 111:6455–6460
Dawson DA, Goldstein RB, Grant BF (2007) Rates and correlates of relapse among individuals in remission from DSM-IV alcohol dependence: a 3-year follow-up. Alcohol Clin Exp Res 31:2036–2045
Dawson DA, Goldstein RB, Chou SP, Ruan WJ, Grant BF (2008) Age at first drink and the first incidence of adult-onset DSM-IV alcohol use disorders. Alcohol Clin Exp Res 32:2149–2160
Di Chiara 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
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 90:7966–7969
Diaz MR, Christian DT, Anderson NJ, McCool BA (2011) Chronic ethanol and withdrawal differentially modulate lateral/basolateral amygdala paracapsular and local GABAergic synapses. J Pharmacol Exp Ther 337:162–170
Dobrossy MD, Furlanetti LL, Coenen VA (2015) Electrical stimulation of the medial forebrain bundle in pre-clinical studies of psychiatric disorders. Neurosci Biobehav Rev 49:32–42
Dziegielewski SF (2010) DSM-IV-TR in action, 2nd edn. Wiley, Hoboken
Ebner SR, Roitman MF, Potter DN, Rachlin AB, Chartoff EH (2010) Depressive-like effects of the kappa opioid receptor agonist salvinorin A are associated with decreased phasic dopamine release in the nucleus accumbens. Psychopharmacology 210:241–252
Eldridge MA, Lerchner W, Saunders RC, Kaneko H, Krausz KW, Gonzalez FJ, Ji B, Higuchi M, Minamimoto T, Richmond BJ (2016) Chemogenetic disconnection of monkey orbitofrontal and rhinal cortex reversibly disrupts reward value. Nat Neurosci 19:37–39
Engel JA, Jerlhag E (2014) Alcohol: mechanisms along the mesolimbic dopamine system. Prog Brain Res 211:201–233
Everitt BJ, Robbins TW (2013) From the ventral to the dorsal striatum: devolving views of their roles in drug addiction. Neurosci Biobehav Rev 37:1946–1954
Exley R, Cragg SJ (2008) Presynaptic nicotinic receptors: a dynamic and diverse cholinergic filter of striatal dopamine neurotransmission. Br J Pharmacol 153(Suppl 1):S283–S297
Falk JL (1966) Schedule-induced polydipsia as a function of fixed interval length. J Exp Anal Behav 9:37–39
Ferris MJ, Calipari ES, Yorgason JT, Jones SR (2013) Examining the complex regulation and drug-induced plasticity of dopamine release and uptake using voltammetry in brain slices. ACS Chem Neurosci 4:693–703
Ferris MJ, Espana RA, Locke JL, Konstantopoulos JK, Rose JH, Chen R, Jones SR (2014) Dopamine transporters govern diurnal variation in extracellular dopamine tone. Proc Natl Acad Sci U S A 111:E2751–E2759
Flusberg BA, Nimmerjahn A, Cocker ED, Mukamel EA, Barretto RP, Ko TH, Burns LD, Jung JC, Schnitzer MJ (2008) High-speed, miniaturized fluorescence microscopy in freely moving mice. Nat Methods 5:935–938
Ford CP (2014) The role of D2-autoreceptors in regulating dopamine neuron activity and transmission. Neuroscience 282:13–22
Gerfen CR, Surmeier DJ (2011) Modulation of striatal projection systems by dopamine. Annu Rev Neurosci 34:441–466
Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ Jr, Sibley DR (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250:1429–1432
Gilpin NW, Richardson HN, Cole M, Koob GF (2008) Vapor inhalation of alcohol in rats. Curr Protoc Neurosci Chapter 9:Unit 9.29
Grace AA, Bunney BS (1983) Intracellular and extracellular electrophysiology of nigral dopaminergic neurons--1. Identification and characterization. Neuroscience 10:301–315
Grace AA, Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: single spike firing. J Neurosci 4:2866–2876
Grace AA, Floresco SB, Goto Y, Lodge DJ (2007) Regulation of firing of dopaminergic neurons and control of goal-directed behaviors. Trends Neurosci 30:220–227
Grant KA, Bennett AJ (2003) Advances in nonhuman primate alcohol abuse and alcoholism research. Pharmacol Ther 100:235–255
Grant KA, Leng X, Green HL, Szeliga KT, Rogers LS, Gonzales SW (2008) Drinking typography established by scheduled induction predicts chronic heavy drinking in a monkey model of ethanol self-administration. Alcohol Clin Exp Res 32:1824–1838
Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, Pickering RP, Ruan WJ, Smith SM, Huang B et al (2015) Epidemiology of DSM-5 alcohol use disorder: results from the national epidemiologic survey on alcohol and related conditions III. JAMA Psychiat 72:757–766
Graybiel AM (1995) The basal ganglia. Trends Neurosci 18:60–62
Graybiel AM (2008) Habits, rituals, and the evaluative brain. Annu Rev Neurosci 31:359–387
Green AS, Grahame NJ (2008) Ethanol drinking in rodents: is free-choice drinking related to the reinforcing effects of ethanol? Alcohol 42:1–11
Griffin WC 3rd, Lopez MF, Yanke AB, Middaugh LD, Becker HC (2009) Repeated cycles of chronic intermittent ethanol exposure in mice increases voluntary ethanol drinking and ethanol concentrations in the nucleus accumbens. Psychopharmacology 201:569–580
Hagman BT, Cohn AM (2011) Toward DSM-V: mapping the alcohol use disorder continuum in college students. Drug Alcohol Depend 118:202–208
Hasin DS, Stinson FS, Ogburn E, Grant BF (2007) Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 64(7):830–842
Healey JC, Winder DG, Kash TL (2008) Chronic ethanol exposure leads to divergent control of dopaminergic synapses in distinct target regions. Alcohol 42:179–190
Hendricson AW, Thomas MP, Lippmann MJ, Morrisett RA (2003) Suppression of L-type voltage-gated calcium channel-dependent synaptic plasticity by ethanol: analysis of miniature synaptic currents and dendritic calcium transients. J Pharmacol Exp Ther 307:550–558
Hernandez G, Trujillo-Pisanty I, Cossette MP, Conover K, Shizgal P (2012) Role of dopamine tone in the pursuit of brain stimulation reward. J Neurosci 32:11032–11041
Humphries MD, Prescott TJ (2010) The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward. Prog Neurobiol 90:385–417
Hwa LS, Chu A, Levinson SA, Kayyali TM, DeBold JF, Miczek KA (2011) Persistent escalation of alcohol drinking in C57BL/6J mice with intermittent access to 20% ethanol. Alcohol Clin Exp Res 35:1938–1947
Imperato A, Di Chiara G (1986) Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther 239:219–228
Karkhanis AN, Rose JH, Huggins KN, Konstantopoulos JK, Jones SR (2015) Chronic intermittent ethanol exposure reduces presynaptic dopamine neurotransmission in the mouse nucleus accumbens. Drug Alcohol Depend 150:24–30
Karkhanis AN, Huggins KN, Rose JH, Jones SR (2016) Switch from excitatory to inhibitory actions of ethanol on dopamine levels after chronic exposure: role of kappa opioid receptors. Neuropharmacology 110:190–197
Kashem MA, Ahmed S, Sarker R, Ahmed EU, Hargreaves GA, McGregor IS (2012) Long-term daily access to alcohol alters dopamine-related synthesis and signaling proteins in the rat striatum. Neurochem Int 61:1280–1288
Kissler JL, Sirohi S, Reis DJ, Jansen HT, Quock RM, Smith DG, Walker BM (2014) The one-two punch of alcoholism: role of central amygdala dynorphins/kappa-opioid receptors. Biol Psychiatry 75:744–782
Köhnke MD, Batra A, Kolb W, Köhnke AM, Lutz U, Schick S, Gaertner I (2005) Association of the dopamine transporter gene with alcoholism. Alcohol Alcohol 40(5):339–342
Kokkinidis L, McCarter BD (1990) Postcocaine depression and sensitization of brain-stimulation reward: analysis of reinforcement and performance effects. Pharmacol Biochem Behav 36:463–471
Koller BH, Smithies O (1992) Altering genes in animals by gene targeting. Annu Rev Immunol 10:705–730
Koob GF (2014) Neurocircuitry of alcohol addiction: synthesis from animal models. Handb Clin Neurol 125:33–54
Koyama S, Brodie MS, Appel SB (2007) Ethanol inhibition of m-current and ethanol-induced direct excitation of ventral tegmental area dopamine neurons. J Neurophysiol 97:1977–1985
Kuzmin A, Chefer V, Bazov I, Meis J, Ogren SO, Shippenberg T, Bakalkin G (2013) Upregulated dynorphin opioid peptides mediate alcohol-induced learning and memory impairment. Transl Psychiatry 3:e310
Laine TP, Ahonen A, Torniainen P, Heikkila J, Pyhtinen J, Rasanen P, Niemela O, Hillbom M (1999) Dopamine transporters increase in human brain after alcohol withdrawal. Mol Psychiatry 4:189–191. 104–185
Lam MP, Marinelli PW, Bai L, Gianoulakis C (2008) Effects of acute ethanol on opioid peptide release in the central amygdala: an in vivo microdialysis study. Psychopharmacology 201:261–271
Land BB, Bruchas MR, Schattauer S, Giardino WJ, Aita M, Messinger D, Hnasko TS, Palmiter RD, Chavkin C (2009) Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking. Proc Natl Acad Sci U S A 106:19168–19173
Le AD, Quan B, Juzytch W, Fletcher PJ, Joharchi N, Shaham Y (1998) Reinstatement of alcohol-seeking by priming injections of alcohol and exposure to stress in rats. Psychopharmacology 135:169–174
Levey AI, Hersch SM, Rye DB, Sunahara RK, Niznik HB, Kitt CA, Price DL, Maggio R, Brann MR, Ciliax BJ (1993) Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies. Proc Natl Acad Sci U S A 90:8861–8865
Li TK, Lumeng L, McBride WJ, Waller MB (1979) Progress toward a voluntary oral consumption model of alcoholism. Drug Alcohol Depend 4:45–60
Lovinger DM (2017) Presynaptic ethanol actions: potential roles in ethanol seeking. In: Grant KA (ed) Neuropharmacology of alcohol, Handbook of experimental pharmacology. Springer, Heidelberg
Macey DJ, Schulteis G, Heinrichs SC, Koob GF (1996) Time-dependent quantifiable withdrawal from ethanol in the rat: effect of method of dependence induction. Alcohol 13:163–170
Majchrowicz E, Mendelson JH (1970) Blood concentrations of acetaldehyde and ethanol in chronic alcoholics. Science 168:1100–1102
Marinelli PW, Lam M, Bai L, Quirion R, Gianoulakis C (2006) A microdialysis profile of dynorphin A(1-8) release in the rat nucleus accumbens following alcohol administration. Alcohol Clin Exp Res 30:982–990
Martinez D, Gil R, Slifstein M, Hwang DR, Huang Y, Perez A, Kegeles L, Talbot P, Evans S, Krystal J et al (2005) Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biol Psychiatry 58:779–786
Meador-Woodruff JH, Damask SP, Watson SJ Jr (1994) Differential expression of autoreceptors in the ascending dopamine systems of the human brain. Proc Natl Acad Sci U S A 91:8297–8301
Melchior JR, Jones SR (2017) Chronic ethanol exposure increases inhibition of optically targeted phasic dopamine release in the nucleus accumbens core and medial shell ex vivo. Mol Cell Neurosci 85:93–104
Melis M, Spiga S, Diana M (2005) The dopamine hypothesis of drug addiction: hypodopaminergic state. Int Rev Neurobiol 63:101–154
Meller E, Bohmaker K, Goldstein M, Basham DA (1993) Evidence that striatal synthesis-inhibiting autoreceptors are dopamine D3 receptors. Eur J Pharmacol 249:R5–R6
Mokdad AH, Marks JS, Stroup DF, Gerberding JL (2004) Actual causes of death in the United States, 2000. JAMA 291:1238–1245
Morikawa H, Morrisett RA (2010) Ethanol action on dopaminergic neurons in the ventral tegmental area: interaction with intrinsic ion channels and neurotransmitter inputs. Int Rev Neurobiol 91:235–288
Morisot N, Ron D (2017) Alcohol-dependent molecular adaptations of the NMDA receptor system. Genes Brain Behav 16:139–148
Nabeshima T, Katoh A, Wada M, Kameyama T (1992) Stress-induced changes in brain met-enkephalin, Leu-enkephalin and dynorphin concentrations. Life Sci 51:211–217
Nealey KA, Smith AW, Davis SM, Smith DG, Walker BM (2011) Kappa-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats. Neuropharmacology 61:35–42
Negus SS, Miller LL (2014) Intracranial self-stimulation to evaluate abuse potential of drugs. Pharmacol Rev 66:869–917
Nicola SM (2010) The flexible approach hypothesis: unification of effort and cue-responding hypotheses for the role of nucleus accumbens dopamine in the activation of reward-seeking behavior. J Neurosci 30:16585–16600
Nimitvilai S, You C, Arora DS, McElvain MA, Vandegrift BJ, Brodie MS, Woodward JJ (2016) Differential effects of toluene and ethanol on dopaminergic neurons of the ventral tegmental area. Front Neurosci 10:434
Nimitvilai S, Uys JD, Woodward JJ, Randall PK, Ball LE, Williams RW, Jones BC, Lu L, Grant KA, Mulholland PJ (2017) Orbitofrontal neuroadaptations and cross-species synaptic biomarkers in heavy-drinking macaques. J Neurosci 37:3646–3660
O’Brien C (2011) Addiction and dependence in DSM-V. Addiction 106:866–867
Okamoto T, Harnett MT, Morikawa H (2006) Hyperpolarization-activated cation current (Ih) is an ethanol target in midbrain dopamine neurons of mice. J Neurophysiol 95:619–626
Penn PE, McBride WJ, Lumeng L, Gaff TM, Li TK (1978) Neurochemical and operant behavioral studies of a strain of alcohol-preferring rats. Pharmacol Biochem Behav 8:475–481
Phillips PE, Stuber GD, Heien ML, Wightman RM, Carelli RM (2003) Subsecond dopamine release promotes cocaine seeking. Nature 422:614–618
Pickens RW, Hatsukami DK, Spicer JW, Svikis DS (1985) Relapse by alcohol abusers. Alcohol Clin Exp Res 9:244–247
Pierce RC, Crawford CA, Nonneman AJ, Mattingly BA, Bardo MT (1990) Effect of forebrain dopamine depletion on novelty-induced place preference behavior in rats. Pharmacol Biochem Behav 36:321–325
Pleil KE, Lowery-Gionta EG, Crowley NA, Li C, Marcinkiewcz CA, Rose JH, McCall NM, Maldonado-Devincci AM, Morrow AL, Jones SR et al (2015a) Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala. Neuropharmacology 99:735–749
Pleil KE, Rinker JA, Lowery-Gionta EG, Mazzone CM, McCall NM, Kendra AM, Olson DP, Lowell BB, Grant KA, Thiele TE et al (2015b) NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. Nat Neurosci 18:545–552
Porrino LJ, Lyons D, Smith HR, Daunais JB, Nader MA (2004) Cocaine self-administration produces a progressive involvement of limbic, association, and sensorimotor striatal domains. J Neurosci 24:3554–3562
Rebec GV, Grabner CP, Johnson M, Pierce RC, Bardo MT (1997) Transient increases in catecholaminergic activity in medial prefrontal cortex and nucleus accumbens shell during novelty. Neuroscience 76:707–714
Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J (2009) Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 373:2223–2233
Renteria R, Buske TR, Morrisett RA (2017) Long-term subregion-specific encoding of enhanced ethanol intake by D1DR medium spiny neurons of the nucleus accumbens. Addict Biol. https://doi.org/10.1111/adb.12526
Rhodes JS, Best K, Belknap JK, Finn DA, Crabbe JC (2005) Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiol Behav 84:53–63
Rhodes JS, Ford MM, Yu CH, Brown LL, Finn DA, Garland T Jr, Crabbe JC (2007) Mouse inbred strain differences in ethanol drinking to intoxication. Genes Brain Behav 6:1–18
Rimondini R, Sommer W, Heilig M (2003) A temporal threshold for induction of persistent alcohol preference: behavioral evidence in a rat model of intermittent intoxication. J Stud Alcohol 64:445–449
Ron D, Barak S (2016) Molecular mechanisms underlying alcohol-drinking behaviours. Nat Rev Neurosci 17:576–591
Rose JH, Karkhanis AN, Chen R, Gioia D, Lopez MF, Becker HC, McCool BA, Jones SR (2016) Supersensitive kappa opioid receptors promotes ethanol withdrawal-related behaviors and reduce dopamine signaling in the nucleus accumbens. Int J Neuropsychopharmacol 19. https://doi.org/10.1093/ijnp/pyv127
Rossetti ZL, Melis F, Carboni S, Diana M, Gessa GL (1992) Alcohol withdrawal in rats is associated with a marked fall in extraneuronal dopamine. Alcohol Clin Exp Res 16:529–532
Rossetti ZL, Isola D, De Vry J, Fadda F (1999) Effects of nimodipine on extracellular dopamine levels in the rat nucleus accumbens in ethanol withdrawal. Neuropharmacology 38:1361–1369
Rothblat DS, Rubin E, Schneider JS (2001) Effects of chronic alcohol ingestion on the mesostriatal dopamine system in the rat. Neurosci Lett 300:63–66
Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA et al (1997) Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell 90:991–1001
Schulteis G, Markou A, Cole M, Koob GF (1995) Decreased brain reward produced by ethanol withdrawal. Proc Natl Acad Sci U S A 92:5880–5884
Schultz W (1998) Predictive reward signal of dopamine neurons. J Neurophysiol 80:1–27
Schultz W (2013) Updating dopamine reward signals. Curr Opin Neurobiol 23:229–238
Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275:1593–1599
Seress L (2007) Comparative anatomy of the hippocampal dentate gyrus in adult and developing rodents, non-human primates and humans. Prog Brain Res 163:23–41
Shnitko TA, Robinson DL (2015) Regional variation in phasic dopamine release during alcohol and sucrose self-administration in rats. ACS Chem Neurosci 6:147–154
Siciliano CA, Calipari ES, Cuzon Carlson VC, Helms CM, Lovinger DM, Grant KA, Jones SR (2015a) Voluntary ethanol intake predicts kappa-opioid receptor supersensitivity and regionally distinct dopaminergic adaptations in macaques. J Neurosci 35:5959–5968
Siciliano CA, Calipari ES, Ferris MJ, Jones SR (2015b) Adaptations of presynaptic dopamine terminals induced by psychostimulant self-administration. ACS Chem Neurosci 6:27–36
Siciliano CA, Calipari ES, Yorgason JT, Lovinger DM, Mateo Y, Jimenez VA, Helms CM, Grant KA, Jones SR (2016a) Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques. Psychopharmacology 233:1435–1443
Siciliano CA, Calipari ES, Yorgason JT, Mateo Y, Helms CM, Lovinger DM, Grant KA, Jones SR (2016b) Chronic ethanol self-administration in macaques shifts dopamine feedback inhibition to predominantly D2 receptors in nucleus accumbens core. Drug Alcohol Depend 158:159–163
Siciliano CA, Locke JL, Mathews TA, Lopez MF, Becker HC, Jones SR (2017) Dopamine synthesis in alcohol drinking-prone and -resistant mouse strains. Alcohol 58:25–32
Silberberg M, Silberberg R (1954) Factors modifying the lifespan of mice. Am J Phys 177:23–26
Soderpalm B, Lof E, Ericson M (2009) Mechanistic studies of ethanol's interaction with the mesolimbic dopamine reward system. Pharmacopsychiatry 42(Suppl 1):S87–S94
Stauffer WR, Lak A, Yang A, Borel M, Paulsen O, Boyden ES, Schultz W (2016) Dopamine neuron-specific Optogenetic stimulation in rhesus macaques. Cell 166:1564–1571. e1566
Steiner H, Gerfen CR (1993) Cocaine-induced c-fos messenger RNA is inversely related to dynorphin expression in striatum. J Neurosci 13:5066–5081
Steiner H, Gerfen CR (1996) Dynorphin regulates D1 dopamine receptor-mediated responses in the striatum: relative contributions of pre- and postsynaptic mechanisms in dorsal and ventral striatum demonstrated by altered immediate-early gene induction. J Comp Neurol 376:530–541
Svingos AL, Chavkin C, Colago EE, Pickel VM (2001) Major coexpression of kappa-opioid receptors and the dopamine transporter in nucleus accumbens axonal profiles. Synapse 42:185–192
Tigges G, Gordon T, McClure H, Hall E, Peters A (1988) Survival rate and life span of rhesus monkeys at the Yerkes regional primate research center. Am J Primatol 15:263–273
Tiihonen J, Kuikka J, Bergstrom K, Hakola P, Karhu J, Ryynanen OP, Fohr J (1995) Altered striatal dopamine re-uptake site densities in habitually violent and non-violent alcoholics. Nat Med 1:654–657
Tupala E, Tiihonen J (2004) Dopamine and alcoholism: neurobiological basis of ethanol abuse. Prog Neuro-Psychopharmacol Biol Psychiatry 28:1221–1247
Tupala E, Halonen P, Tiihonen J (2006) Visualization of the cortical dopamine transporter in type 1 and 2 alcoholics with human whole hemisphere autoradiography. Eur Neuropsychopharmacol 16:552–560
Twining RC, Wheeler DS, Ebben AL, Jacobsen AJ, Robble MA, Mantsch JR, Wheeler RA (2015) Aversive stimuli drive drug seeking in a state of low dopamine tone. Biol Psychiatry 77:895–902
Venniro M, Caprioli D, Shaham Y (2016) Animal models of drug relapse and craving: from drug priming-induced reinstatement to incubation of craving after voluntary abstinence. Prog Brain Res 224:25–52
Vivian JA, Green HL, Young JE, Majerksy LS, Thomas BW, Shively CA, Tobin JR, Nader MA, Grant KA (2001) Induction and maintenance of ethanol self-administration in cynomolgus monkeys (Macaca fascicularis): long-term characterization of sex and individual differences. Alcohol Clin Exp Res 25:1087–1097
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, Fischman MW, Foltin RW, Fowler JS, Abumrad NN, Vitkun S, Logan J, Gatley SJ, Pappas N et al (1997) Relationship between subjective effects of cocaine and dopamine transporter occupancy. Nature 386:827–830
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
Walker BM, Zorrilla EP, Koob GF (2011) Systemic kappa-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats. Addict Biol 16:116–119
Wanat MJ, Willuhn I, Clark JJ, Phillips PE (2009) Phasic dopamine release in appetitive behaviors and drug addiction. Curr Drug Abuse Rev 2:195–213
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
Werling LL, Frattali A, Portoghese PS, Takemori AE, Cox BM (1988) Kappa receptor regulation of dopamine release from striatum and cortex of rats and guinea pigs. J Pharmacol Exp Ther 246:282–286
Wightman RM (1988) Voltammetry with microscopic electrodes in new domains. Science 240:415–420
Wightman RM, Strope E, Plotsky PM, Adams RN (1976) Monitoring of transmitter metabolites by voltammetry in cerebrospinal fluid following neural pathway stimulation. Nature 262:145–146
Yen CH, Yeh YW, Liang CS, Ho PS, Kuo SC, Huang CC, Chen CY, Shih MC, Ma KH, Peng GS et al (2015) Reduced dopamine transporter availability and neurocognitive deficits in male patients with alcohol dependence. PLoS One 10:e0131017
Yen CH, Shih MC, Cheng CY, Ma KH, Lu RB, Huang SY (2016) Incongruent reduction of dopamine transporter availability in different subgroups of alcohol dependence. Medicine (Baltimore) 95:e4048
Yim HJ, Schallert T, Randall PK, Gonzales RA (1998) Comparison of local and systemic ethanol effects on extracellular dopamine concentration in rat nucleus accumbens by microdialysis. Alcohol Clin Exp Res 22:367–374
Yorgason JT, Ferris MJ, Steffensen SC, Jones SR (2014) Frequency-dependent effects of ethanol on dopamine release in the nucleus accumbens. Alcohol Clin Exp Res 38:438–447
Yorgason JT, Rose JH, McIntosh JM, Ferris MJ, Jones SR (2015) Greater ethanol inhibition of presynaptic dopamine release in C57BL/6J than DBA/2J mice: role of nicotinic acetylcholine receptors. Neuroscience 284:854–864
Acknowledgments
This work was funded by NIH grants U01 AA014091, R01 AA021099, P01 AA023299 (SRJ), T32 AA007565 (CAS, ANK, KMH, JRM), F31 DA037710, F32 MH111216, Brain and Behavior Research Foundation (CAS), K01 AA023874 (ANK), and F31 AA023144 (JRM).
Financial Disclosure: The authors declare no competing financial interests.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this chapter
Cite this chapter
Siciliano, C.A., Karkhanis, A.N., Holleran, K.M., Melchior, J.R., Jones, S.R. (2018). Cross-Species Alterations in Synaptic Dopamine Regulation After Chronic Alcohol Exposure. In: Grant, K., Lovinger, D. (eds) The Neuropharmacology of Alcohol . Handbook of Experimental Pharmacology, vol 248. Springer, Cham. https://doi.org/10.1007/164_2018_106
Download citation
DOI: https://doi.org/10.1007/164_2018_106
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-96522-2
Online ISBN: 978-3-319-96523-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)