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. The aim of the present study was to examine the effects of a range of compounds known to influence 5-HT neurotransmission, including selective 5-HT receptor agonists and antagonists, on ethanol ingestion and maintained behaviour in an operant self-administration paradigm. Female Sprague-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/kg of body weight), and locomotor activity (LMA) were measured following administration of 5-HT agonists (5-HT, d-fenfluramine, fluoxetine, buspirone, TFMPP, and DOI) and antagonists (metergoline, ritanserin, and ondansetron) 30 min prior to testing. d-Fenfluramine, fluoxetine, buspirone, TFMPP, and DOI all produced a reduction in ethanol ingestion and maintained behaviour at doses that failed to reduce LMA. Conversely, metergoline and ritanserin only reduced ethanol self-administration at doses that concomitantly reduced LMA. 5-HT and ondansetron were without effect on any measure. These results demonstrate that, under the present experimental conditions, activation of central 5-HT1A, 5-HT1B, and 5-HT2 receptors reduced ethanol intake and reinforced behaviour in an operant paradigm.
Wilson
A W
AW
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, West Yorkshire, UK. alex_w_wilson@sbphrd.com
Neill
J C
JC
Costall
B
B
D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005277:Fenfluramine / Q000031:analogs & derivatives / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D008711:Metergoline / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016713:Ritanserin / Q000494:pharmacology; D012646:Self Administration; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors
D002065:Buspirone; D000431:Ethanol; D005277:Fenfluramine; D005473:Fluoxetine; D008711:Metergoline; D017294:Ondansetron; D010879:Piperazines; D016713:Ritanserin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C018406:1-(3-trifluoromethylphenyl)piperazine