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Striatal Involvement in Human Alcoholism and Alcohol Consumption, and Withdrawal in Animal Models

Authors

  • Gang Chen,

    1. From the Department of Behavioral Neuroscience and Portland Alcohol Research Center (GC, KJB), Portland Veterans Affairs Medical Center and Oregon Health and Science University, Portland, Oregon; Laboratory for Integrative Neuroscience (VCCC, DML), National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; Ernest Gallo Research Center (JW, DR), Department of Neurology, University of California, San Francisco, California; and Department of Psychiatry and Psychotherapy (AB, AH), Charité—Universitätsmedizin, Berlin, Germany.
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  • Verginia C. Cuzon Carlson,

    1. From the Department of Behavioral Neuroscience and Portland Alcohol Research Center (GC, KJB), Portland Veterans Affairs Medical Center and Oregon Health and Science University, Portland, Oregon; Laboratory for Integrative Neuroscience (VCCC, DML), National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; Ernest Gallo Research Center (JW, DR), Department of Neurology, University of California, San Francisco, California; and Department of Psychiatry and Psychotherapy (AB, AH), Charité—Universitätsmedizin, Berlin, Germany.
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  • Jun Wang,

    1. From the Department of Behavioral Neuroscience and Portland Alcohol Research Center (GC, KJB), Portland Veterans Affairs Medical Center and Oregon Health and Science University, Portland, Oregon; Laboratory for Integrative Neuroscience (VCCC, DML), National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; Ernest Gallo Research Center (JW, DR), Department of Neurology, University of California, San Francisco, California; and Department of Psychiatry and Psychotherapy (AB, AH), Charité—Universitätsmedizin, Berlin, Germany.
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  • Anne Beck,

    1. From the Department of Behavioral Neuroscience and Portland Alcohol Research Center (GC, KJB), Portland Veterans Affairs Medical Center and Oregon Health and Science University, Portland, Oregon; Laboratory for Integrative Neuroscience (VCCC, DML), National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; Ernest Gallo Research Center (JW, DR), Department of Neurology, University of California, San Francisco, California; and Department of Psychiatry and Psychotherapy (AB, AH), Charité—Universitätsmedizin, Berlin, Germany.
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  • Andreas Heinz,

    1. From the Department of Behavioral Neuroscience and Portland Alcohol Research Center (GC, KJB), Portland Veterans Affairs Medical Center and Oregon Health and Science University, Portland, Oregon; Laboratory for Integrative Neuroscience (VCCC, DML), National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; Ernest Gallo Research Center (JW, DR), Department of Neurology, University of California, San Francisco, California; and Department of Psychiatry and Psychotherapy (AB, AH), Charité—Universitätsmedizin, Berlin, Germany.
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  • Dorit Ron,

    1. From the Department of Behavioral Neuroscience and Portland Alcohol Research Center (GC, KJB), Portland Veterans Affairs Medical Center and Oregon Health and Science University, Portland, Oregon; Laboratory for Integrative Neuroscience (VCCC, DML), National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; Ernest Gallo Research Center (JW, DR), Department of Neurology, University of California, San Francisco, California; and Department of Psychiatry and Psychotherapy (AB, AH), Charité—Universitätsmedizin, Berlin, Germany.
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  • David M. Lovinger,

    1. From the Department of Behavioral Neuroscience and Portland Alcohol Research Center (GC, KJB), Portland Veterans Affairs Medical Center and Oregon Health and Science University, Portland, Oregon; Laboratory for Integrative Neuroscience (VCCC, DML), National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; Ernest Gallo Research Center (JW, DR), Department of Neurology, University of California, San Francisco, California; and Department of Psychiatry and Psychotherapy (AB, AH), Charité—Universitätsmedizin, Berlin, Germany.
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  • Kari J. Buck

    1. From the Department of Behavioral Neuroscience and Portland Alcohol Research Center (GC, KJB), Portland Veterans Affairs Medical Center and Oregon Health and Science University, Portland, Oregon; Laboratory for Integrative Neuroscience (VCCC, DML), National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; Ernest Gallo Research Center (JW, DR), Department of Neurology, University of California, San Francisco, California; and Department of Psychiatry and Psychotherapy (AB, AH), Charité—Universitätsmedizin, Berlin, Germany.
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Reprint requests: Gang Chen, PhD, Institute of Translational Neuroscience, RM 4-140, MBB 2101 6th SE, East Campus, University of Minnesota, Minneapolis, MN 55455; Tel.: +1-612-626-5079; Fax: +1-612-626-2032; E-mail: hdn_2001@yahoo.com

Abstract

Background:  Different regions of the striatum may have distinct roles in acute intoxication, alcohol seeking, dependence, and withdrawal.

Methods:  The recent advances are reviewed and discussed in our understanding of the role of the dorsolateral striatum (DLS), dorsomedial striatum (DMS), and ventral striatum in behavioral responses to alcohol, including alcohol craving in abstinent alcoholics, and alcohol consumption and withdrawal in rat, mouse, and nonhuman primate models.

Results:  Reduced neuronal activity as well as dysfunctional connectivity between the ventral striatum and the dorsolateral prefrontal cortex is associated with alcohol craving and impairment of new learning processes in abstinent alcoholics. Within the DLS of mice and nonhuman primates withdrawn from alcohol after chronic exposure, glutamatergic transmission in striatal projection neurons is increased, while GABAergic transmission is decreased. Glutamatergic transmission in DMS projection neurons is also increased in ethanol withdrawn rats. Ex vivo or in vivo ethanol exposure and withdrawal causes a long-lasting increase in NR2B subunit-containing NMDA receptor activity in the DMS, contributing to ethanol drinking. Analyses of neuronal activation associated with alcohol withdrawal and site-directed lesions in mice implicate the rostroventral caudate putamen, a ventrolateral segment of the DMS, in genetically determined differences in risk for alcohol withdrawal involved in physical association of the multi-PDZ domain protein, MPDZ, with 5-HT2C receptors and/or NR2B.

Conclusions:  Alterations of dopaminergic, glutamatergic, and GABAergic signaling within different regions of the striatum by alcohol is critical for alcohol craving, consumption, dependence, and withdrawal in humans and animal models.

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