Volume 35, Issue 10 pp. 1739-1748

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

Gang Chen

Gang Chen

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.

Search for more papers by this author
Verginia C. Cuzon Carlson

Verginia C. Cuzon Carlson

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.

Search for more papers by this author
Jun Wang

Jun Wang

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.

Search for more papers by this author
Anne Beck

Anne Beck

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.

Search for more papers by this author
Andreas Heinz

Andreas Heinz

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.

Search for more papers by this author
Dorit Ron

Dorit Ron

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.

Search for more papers by this author
David M. Lovinger

David M. Lovinger

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.

Search for more papers by this author
Kari J. Buck

Kari J. Buck

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.

Search for more papers by this author
First published: 25 May 2011
Citations: 80
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: [email protected]

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.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.