Cross-Species Alterations in Synaptic Dopamine Regulation After Chronic Alcohol Exposure
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.
KeywordsAlcohol Autoreceptors Cross-species Dopamine Kappa Opioid receptors Monkey Mouse Nonhuman primate Rat Uptake
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.
- 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 36:2513–2528PubMedPubMedCentralGoogle Scholar
- Dziegielewski SF (2010) DSM-IV-TR in action, 2nd edn. Wiley, HobokenGoogle Scholar
- 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 72:757–766Google Scholar
- 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 75:744–782Google Scholar
- 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 106:19168–19173PubMedPubMedCentralGoogle Scholar
- Lovinger DM (2017) Presynaptic ethanol actions: potential roles in ethanol seeking. In: Grant KA (ed) Neuropharmacology of alcohol, Handbook of experimental pharmacology. Springer, HeidelbergGoogle Scholar
- 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 99:735–749PubMedPubMedCentralGoogle Scholar
- 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
- 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
- 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 233:1435–1443PubMedPubMedCentralGoogle Scholar
- Silberberg M, Silberberg R (1954) Factors modifying the lifespan of mice. Am J Phys 177:23–26Google Scholar
- 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 15:263–273Google Scholar
- Tupala E, Tiihonen J (2004) Dopamine and alcoholism: neurobiological basis of ethanol abuse. Prog Neuro-Psychopharmacol Biol Psychiatry 28:1221–1247Google Scholar
- 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 25:1087–1097PubMedGoogle Scholar
- 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:e4048Google Scholar