5-HT1A receptor blockade and the motivational profile of ethanol

Although several serotonin (5-HT) receptor subtypes influence ethanol consumption, the motivational mechanisms underlying these changes remain unclear. The present experiments characterized the rewarding, aversive and stimulant effects of ethanol in combination with a specific 5-HT1A receptor antagonist (pindobind-5HT1A). In a place conditioning study, adult male Swiss-Webster mice received 6 parings of a distinctive tactile stimulus with either 2 g/kg ethanol, 2.5 mg/kg pindobind-5HT1A, or both drugs in combination. Ethanol-conditioned preference for the tactile cue was enhanced in mice also receiving pindobind-5HT1A, which did not produce cue preference in the absence of ethanol. In a taste conditioning study, Swiss-Webster mice received 4 trials consisting of access to a distinctive NaCl flavor followed by either 4 g/kg ethanol, 2.5 mg/kg pindobind-5HT1A, or both drugs. As expected, ethanol produced avoidance of the flavor. Pindobind-5HT1A did not reduce or enhance ethanol-conditioned flavor aversion. In a study characterizing locomotor activity, 2 g/kg ethanol produced stimulation, which was enhanced after 10 daily treatments. Locomotor sensitization was not altered by co-treatment with pindobind-5HT1A. Overall, the present results show specific effects of 5-HT1A blockade on ethanol reward.