Microdialysis assessment of the impact of (+)3,4‐methylenedioxymethamphetamine, cocaine, and cocaethylene on serotonergic neurons
Drug Development Research September 1, 1994 DOI: 10.1002/ddr.430330102 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Microdialysis study Peer reviewed |
|---|---|
| Population | Rat brain tissue (dorsal raphe slices) and chloral hydrate-anesthetized rats |
| Interventions | (+)3 ecstasy) Cocaine Cocaethylene Fluoxetine Tryptophan |
| Topics | MDMA Serotonin |
| Citations | 14 |
| Key points | The authors propose that (+)‑MDMA inhibits serotonin neuronal firing by releasing serotonin that acts on somatodendritic autoreceptors, supported by fluoxetine blocking and tryptophan enhancing release. Cocaine and cocaethylene differed by route: intravenously, both raised dopamine equally but only cocaine raised serotonin; intraperitoneally, cocaethylene raised serotonin but cocaine was more potent, with cocaethylene brain levels half those of cocaine. |
Abstract
Abstract 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. © 1994 Wiley‐Liss, Inc.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.