AN INVESTIGATION INTO THE EFFECTS OF 5-HT AGONISTS AND RECEPTOR ANTAGONISTS ON ETHANOL SELF-ADMINISTRATION IN THE RAT

Pharmacological manipulation leading to altered 5-HT function has been widely demonstrated to reduce ethanol intake in free choice tests. Th e aim of the present study was to examine the effects of a range of co mpounds known to influence 5-HT neurotransmission, including selective 5-HT receptor agonists and antagonists, on ethanol ingestion and main tained behaviour in an operant self-administration paradigm. Female Sp rague-Dawley rats were trained to respond for 8% ethanol (v/v) in a 60 -min test by a previously described technique. The number of responses and ethanol reinforcers (dipper deliveries), ethanol consumption (g/k g of body weight), and locomotor activity (LMA) were measured followin g administration of 5-HT agonists (5-HT, d-fenfluramine, fluoxetine, b uspirone, TFMPP, and DOI) and antagonists (metergoline, ritanserin, an d ondansetron) 30 min prior to testing. d-Fenfluramine, fluoxetine, bu spirone, TFMPP, and DOI all produced a reduction in ethanol ingestion and maintained behaviour at doses that failed to reduce LIVIA. Convers ely, metergoline and ritanserin only reduced ethanol self-administrati on at doses that concomitantly reduced LMA. 5-HT and ondansetron were without effect on any measure. These results demonstrate that, under t he present experimental conditions, activation of central 5-HT1A, 5-HT 1B, and 5-HT2 receptors reduced ethanol intake and reinforced behaviou r in an operant paradigm. (C) 1998 Elsevier Science Inc..