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Drug Alcohol Depend. 2016 Jan 1;158:159-63. doi: 10.1016/j.drugalcdep.2015.10.031. Epub 2015 Nov 10.

Chronic ethanol self-administration in macaques shifts dopamine feedback inhibition to predominantly D2 receptors in nucleus accumbens core.

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Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States.
Laboratory for Integrative Neuroscience, Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, MD, United States.
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, United States.
Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States. Electronic address:



Given the high level of homology between nonhuman primates and humans in regard to anatomy, physiology and ethanol drinking patterns, nonhuman primates represent an unparalleled preclinical model for examining the neurobiological basis of ethanol abuse.


Here we examined the neurochemical consequences of chronic daily ethanol use using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core or dorsolateral caudate taken from male cynomolgus macaques following ethanol drinking.


We found that in both regions the ability of ethanol to decrease dopamine release was unchanged, indicating that ethanol self-administration does not produce tolerance or sensitization to ethanol effects on dopamine release at the dopamine terminal at this time point. We also found that in the nucleus accumbens core, autoregulation of dopamine release was shifted from equal D2 and D3 receptor involvement in control animals to primarily D2 receptor-mediated in drinkers. Specifically, the effect quinpirole, a D2/D3 receptor agonist, on dopamine release was equal across groups; however, dopamine signals were reversed to a greater extent by the selective D3 receptor antagonist SB-277,011A in control animals, indicating a greater contribution of D2 receptors in quinpirole-induced inhibition following ethanol self-administration. In the dorsolateral caudate, the effects of quinpirole and reversal with SB-277,011A was not different between ethanol and control slices.


This work provides novel insight into the dopaminergic adaptations resulting from chronic ethanol use in nonhuman primates and indicates that alterations in D2/D3 dopamine autoreceptor signaling may be an important neurochemical adaptation to ethanol consumption during early use.


Autoreceptor; Caudate; D3; Macaque; Monkey; Nucleus accumbens

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