Involvement of the mesopallidal dopamine system in the biological and reinforcing effects of ethanol

Roberto Ildefonso Melendez, Purdue University

Abstract

It has become increasingly clear that the ventral pallidum (VP) plays a critical role in the nurobiological processes underlying reinforcement. Recently, the mesopallidal dopamine system has been shown to be involved in the biological and reinforcing effects of cocaine. However, the role of the mesopallidal dopamine system in the actions of other drugs of abuse, including alcohol, remains largely unexplored. The present study was designed to test the hypothesis that the mesopallidal dopamine system is involved in the biological and reinforcing effects of ethanol. To test this hypothesis, several experimental techniques were employed, including dual-probe microdialysis, microdialysis paired with operant responding, reverse microdialysis, and intracranial microinjections paired with ethanol self-administration. The findings indicate that (1) systemic ethanol administration increases the extracellular levels of dopamine in the VP but not in the globus pallidus (i.e., dorsal pallidum), (2) anticipation and self-administration of ethanol increases the extracellular levels of dopamine in the VP, (3) blockade of VP-dopamine D2 but not D1 receptors increases ethanol self-administration, and (4) VP-dopamine D1 and D2 receptors regulate the extracellular levels of dopamine in the VP. Together, these findings support the hypothesis that the mesopallidal dopamine system is involved in the biological and reinforcing effects of ethanol. Furthermore, the findings provide novel evidence in support of the inclusion of the VP in the actions of drugs of abuse and this brain region may be a critical element in addiction.

Degree

Ph.D.

Advisors

Murphy, Purdue University.

Subject Area

Psychobiology|Pharmacology

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