Striatal Involvement in Human Alcoholism and Alcohol Consumption, and Withdrawal in Animal Models
Article first published online: 25 MAY 2011
Copyright © 2011 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 35, Issue 10, pages 1739–1748, October 2011
How to Cite
Chen, G., Cuzon Carlson, V. C., Wang, J., Beck, A., Heinz, A., Ron, D., Lovinger, D. M. and Buck, K. J. (2011), Striatal Involvement in Human Alcoholism and Alcohol Consumption, and Withdrawal in Animal Models. Alcoholism: Clinical and Experimental Research, 35: 1739–1748. doi: 10.1111/j.1530-0277.2011.01520.x
- Issue published online: 26 SEP 2011
- Article first published online: 25 MAY 2011
- Received for publication November 30, 2010; accepted February 1, 2011.
- Fyn Kinase;
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 Within the DLS of mice and nonhuman primates withdrawn from alcohol after chronic exposure, glutamatergic transmission in striatal projection neurons is increased, while GABAergic transmission is decreased. Glutamatergic transmission in DMS projection neurons is also increased in ethanol withdrawn rats.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.