Inhibition of 5-HT neurotransmission increases clonidine protective effects on naloxone-induced conditioned placeaversion in morphine-dependent rats

Abstract

Previous pharmacologicalstudies 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-total5,7-dihydroxytryptamine-induced lesion (90%depletion) or (ii) an acute serotonin (5-HT) inhibition induced by the specific stimulation of 5-HTIA autoreceptors (8-OHDPAT 5100 mg/kg), on naloxone-induced conditioned place aversion in morphine-dependent rats. Morphine dependence was induced by theimplantation of morphine slow-release pellets. The protective properties of clonidine (an alpha-2 adrenergic agonist classically given foropiate detoxification) were also tested after inhibition of 5-HT transmission. Serotonergic lesions in morphine-dependent rats failed toalter naloxone-induced conditioned place aversion but increased the sensitivity to the protective effects of clonidine. Acuteneuropharmacologicalblockade of serotonin transmission also potentiated the clonidine effects on naloxone-induced conditioned placeaversion. When combined with the 5-HTIA agonist 8-OHDPAT, clonidine was also found to be more potent. Further understanding ofthis serotonin/noradrenaline interaction might help devise new therapeutic treatments for the acute opiate withdrawalsyndrome. © 2003 Nature Publishing Group.