The COMT inhibitor Tolcapone suppresses cue-evoked drinking in alcohol preferring P rats
Abstract
Dopamine (DA) has been shown to play a central role in regulating motivated behavior and encoding reward. Chronic drug abuse elicits a state of hypodopaminergia in the mesocorticolimbic system in both humans and preclinical rodent models of addiction, including those modeling alcohol use disorders (AUD). Working under the hypothesis that reductions in the bioavailability of DA play an integral role in the expression of the excessive drinking phenotype, the COMT inhibitor Tolcapone was used as a means to increase DA efflux and drinking behaviors were then assessed. Sucrose and ethanol consumption were measured in alcohol preferring (P) and Wistar rats in both a free choice drinking protocol and a novel cued access protocol. Tolcapone attenuated the consumption of ethanol, and to a lesser extent sucrose, in P rats in the cued access protocol while no effect was observed in the free choice drinking protocol. Tolcapone also decreased ethanol consumption in high drinking Wistar rats. A follow-up experiment using the DA agonist D-amphetamine (AMPH) showed no change in ethanol consumption. Collectively, these data suggest that COMT inhibitors may be capable of alleviating the extremely motivating or salient nature of stimuli associated with alcohol. The hypothesis is put forth that the relative specificity of Tolcapone for cortical DA systems may mediate the suppression of the high seeking/drinking phenotype.
Degree
M.S.
Advisors
Czachowski, Purdue University.
Subject Area
Neurosciences|Behavioral psychology|Pharmacology
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