1. ¹Lab de Neuropsychobiologie des Désadaptations, Université de Bordeaux II, Bordeaux, France
2. ²Depto de Fisiologia Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain
3. ³Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, USA

Correspondence: Dr S Caillé, Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA. Tel: 858-784-7305; Fax: 858-784-7405; E-mail: scaille@scripps.edu

Received 13 April 2002; Revised 5 July 2002; Accepted 10 July 2002.

Abstract

Previous pharmacological studies have implicated serotonergic brain systems in opiate-withdrawal-precipitated conditioned place aversion. To assess this hypothesis, we tested the effects of either (i) a near-total 5,7-dihydroxytryptamine-induced lesion (90% depletion) or (ii) an acute serotonin (5-HT) inhibition induced by the specific stimulation of 5-HT1A autoreceptors (8-OHDPAT 5–100 g/kg), on naloxone-induced conditioned place aversion in morphine-dependent rats. Morphine dependence was induced by the implantation of morphine slow-release pellets. The protective properties of clonidine (an alpha-2 adrenergic agonist classically given for opiate detoxification) were also tested after inhibition of 5-HT transmission. Serotonergic lesions in morphine-dependent rats failed to alter naloxone-induced conditioned place aversion but increased the sensitivity to the protective effects of clonidine. Acute neuropharmacological blockade of serotonin transmission also potentiated the clonidine effects on naloxone-induced conditioned place aversion. When combined with the 5-HT1A agonist 8-OHDPAT, clonidine was also found to be more potent. Further understanding of this serotonin/noradrenaline interaction might help devise new therapeutic treatments for the acute opiate withdrawal syndrome.