THE 5-HT(3) ANTAGONIST ZACOPRIDE ATTENUATES COCAINE-INDUCED INCREASESIN EXTRACELLULAR DOPAMINE IN RAT NUCLEUS-ACCUMBENS

Pretreatment with the serotonin-3 (5-HT3) antagonist racemic (+/-)-Zac opride hydrochloride (ZAC, 0.1 mg/kg, IP) has been previously found to completely abolish the locomotor activity induced by cocaine (10 mg/k g, IP). To determine if this effect was mediated by fluctuations in th e extracellular levels of forebrain dopamine (DA), we examined the abi lity of ZAC to attenuate cocaine-induced increases in extracellular DA levels. Microdialysis samples were collected from the nucleus accumbe ns region (NAS) of awake, mate, Sprague-Dawley rats. ZAC treatment alo ne (0.1 mg/kg, IP) did not alter DA levels relative to baseline. Howev er, this dose of ZAC given 1 h prior to cocaine challenge (10 mg/kg, I P) caused a 27% reduction in the peak level of extracellular DA produc ed by cocaine, relative to saline-pretreated control animals. These re sults suggest that the ability of ZAC to attenuate cocaine-induced inc reases in extracellular DA levels may contribute to ZAC's ability to s uppress cocaine-induced locomotor activity in the rat. However, additi onal neurochemical mechanisms are likely to be important in mediating the robust behavioral effects previously reported.