MICRODIALYSIS ASSESSMENT OF THE IMPACT OF (+)3,4-METHYLENEDIOXYMETHAMPHETAMINE, COCAINE, AND COCAETHYLENE ON SEROTONERGIC NEURONS

This overview summarizes the results of microdialysis studies into the effects of several psychoactive drugs on extracellular serotonin (5-HT) levels in rat brain. The effects of (+)3,4-methylenedioxymethamphetamine (MDMA, ecstasy) were examined in the brain slice preparation for comparison with parallel electrophysiological studies of the impact of (+)-MDMA on dorsal raphe 5-HT neuronal firing. (+)-MDMA induced the release of 5-HT from slices of dorsal raphe. The release was inhibited by fluoxetine, and augmented by tryptophan pretreatment. The results support a mechanism of action whereby (+)-MDMA inhibits 5-HT neuronal firing by releasing 5-HT which then acts upon somatodendritic autoreceptors. In other studies, the effects of cocaine and cocaethylene (the psychoactive metabolite of concurrent cocaine/ethanol consumption) on extracellular 5-HT and dopamine levels in the chloral hydrate-anesthetized rat were examined. Both the intravenous and intraperitoneal routes were examined. By intravenous route, both drugs had equivalent effect at increasing dopamine levels. Cocaine significantly increased 5-HT levels, while cocaethylene had no impact. By intraperitoneal route, cocaethylene was able to increase 5-HT levels, but cocaine remained more potent. Route-dependent differences in bioavailability were evident from studies of brain levels using microdialysis. By intravenous administration, equivalent amounts of both drugs entered the brain, whereas by intraperitoneal route, levels of cocaethylene were half those of cocaine. (C) 1994 Wiley-Liss, Inc.