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      Voluntary ethanol intake predicts κ-opioid receptor supersensitivity and regionally distinct dopaminergic adaptations in macaques.

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          Abstract

          The dopaminergic projections from the ventral midbrain to the striatum have long been implicated in mediating motivated behaviors and addiction. Previously it was demonstrated that κ-opioid receptor (KOR) signaling in the striatum plays a critical role in the increased reinforcing efficacy of ethanol following ethanol vapor exposure in rodent models. Although rodents have been used extensively to determine the neurochemical consequences of chronic ethanol exposure, establishing high levels of voluntary drinking in these models has proven difficult. Conversely, nonhuman primates exhibit similar intake and pattern to humans in regard to drinking. Here we examine the effects of chronic voluntary ethanol self-administration on dopamine neurotransmission and the ability of KORs to regulate dopamine release in the dorsolateral caudate (DLC) and nucleus accumbens (NAc) core. Using voltammetry in brain slices from cynomolgus macaques after 6 months of ad libitum ethanol drinking, we found increased KOR sensitivity in both the DLC and NAc. The magnitude of ethanol intake predicted increases in KOR sensitivity in the NAc core, but not the DLC. Additionally, ethanol drinking increased dopamine release and uptake in the NAc, but decreased both of these measures in the DLC. These data suggest that chronic daily drinking may result in regionally distinct disruptions of striatal outputs. In concert with previous reports showing increased KOR regulation of drinking behaviors induced by ethanol exposure, the strong relationship between KOR activity and voluntary ethanol intake observed here gives further support to the hypothesis that KORs may provide a promising pharmacotherapeutic target in the treatment of alcoholism.

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          Author and article information

          Journal
          J. Neurosci.
          The Journal of neuroscience : the official journal of the Society for Neuroscience
          1529-2401
          0270-6474
          Apr 15 2015
          : 35
          : 15
          Affiliations
          [1 ] Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157.
          [2 ] Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, and.
          [3 ] Laboratory for Integrative Neuroscience, Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20832.
          [4 ] Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, srjones@wakehealth.edu.
          Article
          35/15/5959
          10.1523/JNEUROSCI.4820-14.2015
          4397597
          25878269
          d2e92693-bcc1-44c5-822d-3bc699bc1d4d
          Copyright © 2015 the authors 0270-6474/15/355959-10$15.00/0.
          History

          caudate,dopamine,nonhuman primate,nucleus accumbens,voltammetry,κ-opioid receptor

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