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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on August 2, 2005; DOI: 10.1124/jpet.105.084350

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Received for publication February 2, 2005.
Revised July 27, 2005.
Accepted for publication July 28, 2005.

Prolonged Increase in the Sensitivity of the Posterior Ventral Tegmental Area to the Reinforcing Effects of Ethanol Following Repeated Exposure to Cycles of Ethanol Access and Deprivation

Zachary A Rodd 1*, Richard L. Bell 1, Victoria K. McQueen 1, Michelle R. Davids 1, Cathleen C. Hsu 1, James M. Murphy 2, Ting-Kai Li 3, Lawrence Lumeng 1, William J. McBride 1

1 Indiana University: School of Medicine 2 Indiana University-Purdue University at Indianapolis 3 National Institute on Alcohol Abuse

* Address correspondence to: E-mail: zrodd{at}iupui.edu

Abstract

The posterior ventral tegmental area (VTA) is a neuroanatomical substrate mediating the reinforcing effects of ethanol in rats. Repeated alcohol deprivations produce robust ethanol intakes of alcohol-preferring (P) rats during relapse and increase the reinforcing effects of oral alcohol self-administration. The objective of this study was to test the hypothesis that alcohol drinking and repeated alcohol deprivations will increase the reinforcing effects of ethanol within the posterior VTA of P rats. Groups of female P rats were used (alcohol-naive, continuous access, and repeatedly deprived). Each rat was implanted with a guide cannula aimed at the posterior VTA. Depression of the active lever produced the infusion of 100 nl of artificial CSF or ethanol (25- 300 mg%). Each rat was given only one ethanol concentration during the 4-hr sessions conducted every other day. Compared to the infusions of artificial CSF, the alcohol-naive group reliably self-infused 75 and 150 mg% ethanol, but not the lower or higher concentrations. On the other hand, the continuous access group had significantly higher self-infusions of 50, 75, 150 and 300 mg% ethanol compared to artificial CSF infusions. The repeatedly deprived group also self-infused significantly more of 50, 75, 150 and 300 mg% ethanol than artificial CSF; moreover, the number of infusions for all 4 concentrations was higher in the repeatedly deprived versus the continuous access group. Chronic alcohol drinking by P rats increased the reinforcing effects of ethanol within the posterior VTA and repeated alcohol deprivations produced a further increase in these reinforcing effects of ethanol.


Key words: alcohol-preferring P rats, ethanol reinforcement, intracranial self-administration, neuroadaptations, repeated alcohol deprivations, ventral tegmental area




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