Cyclo-oxygenase-inhibitors increase morphine effects on mesolimbic dopamine neurons

The effect of cyclo-oxygenase inhibitors, indomethacin and nimesulide, on t he action of i.v. morphine on dopamine neurons projecting to the nucleus Ac cumbens was studied using standard extracellular recording techniques coupl ed with antidromic identification in unanesthetized rats. The i.v. administ ration of either nimesulide (3 mg/kg) or indomethacin (3.5 mg/kg) per se di d not affect the firing rate of mesolimbic dopamine cells. In contrast, the subsequent administration of morphine (0.25-2 mg/kg i.v.) potently increas ed the firing rate of mesolimbic dopamine neurons in cyclo-oxygenase inhibi tor-pretreated rats as compared with saline-pretreated rats. The maximal en hancement of basal firing rare at the highest dose of morphine tested was 9 2%, 80% and 47%, for nimesulide-, indomethacin-, and saline-treated rats, r espectively. Our results indicate that the effect of morphine on mesolimbic dopamine cells is potentiated by blocking cyclo-oxygenase activity and sug gest that the modulation of cyclo-oxygenase pathway in dopamine cells might be involved in the cellular mechanisms of the rewarding actions of morphin e. (C) 2000 Elsevier Science B.V. All rights reserved.