An Investigation Into the Effects of 5-HT Agonists and Receptor Antagonists on Ethanol Self-Administration in the Rat

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 1998-10, Vol.16 (3), p.249-270
• Main Authors: Wilson, A.W., Neill, J.C., Costall, B.
• Format: Article
• Language: English
• Subjects: 5-Hydroxytryptamine; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Buspirone; Buspirone - pharmacology; d-Fenfluramine; DOI; Dose-Response Relationship, Drug; Ethanol; Ethanol - metabolism; Female; Fenfluramine - analogs & derivatives; Fenfluramine - pharmacology; Fluoxetine; Fluoxetine - pharmacology; Limited access paradigm; Medical sciences; Metergoline; Metergoline - pharmacology; Ondansetron; Ondansetron - pharmacology; Operant; Oral self-administration; Piperazines - pharmacology; Rats; Rats, Sprague-Dawley; Ritanserin; Ritanserin - pharmacology; Self Administration; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Serotonin Uptake Inhibitors - pharmacology; Sprague–Dawley rats; TFMPP; Time Factors; Toxicology
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/S0741-8329(98)00013-5

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-HT 1A, 5-HT 1B, and 5-HT 2 receptors reduced ethanol intake and reinforced behaviour in an operant paradigm.