Serotonin release contributes to the locomotor stimulant effects of 3,4-methylenedioxymethamphetamine in rats.
C. Callaway, Lauren L. Wing, Mark A. Geyer, Departmentof Psychiatry, Ucsdschoolof Medicine, Californiaandnimh Lajolla, L. L. W. Neurosciencecenter, St Elizabeth 'S Hospital, D. Washington
Journal of Pharmacology and Experimental Therapeutics August 1, 1990 DOI: 10.1016/s0022-3565(25)12637-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | S-(+)MDMA fluoxetine sertraline zimelidine p-chlorophenylalanine (+)amphetamine |
| Topics | MDMA Serotonin |
| Key findings | The authors conclude that (+)MDMA-induced locomotor hyperactivity in rats depends on release of endogenous central serotonin, since selective serotonin uptake inhibitors and serotonin depletion attenuated it while catecholamine synthesis inhibition did not, and that this mechanism is qualitatively different from that of (+)amphetamine. |
Abstract
Methylenedioxymethamphetamine (MDMA) is a phenylethylamine with novel mood-altering properties in humans. MDMA shares the dopamine-releasing properties of amphetamine but has been found to be a more potent releaser of serotonin (5-HT). The present study undertook to determine the relative roles of dopamine and 5-HT release in MDMA-induced locomotor hyperactivity. S-(+)MDMA produced dose-dependent increases of rat locomotion. Investigatory behaviors such as holepokes and rearings were suppressed by (+)MDMA. Pretreatment with the selective 5-HT uptake inhibitors fluoxetine, sertraline and zimelidine inhibited (+)MDMA-induced locomotor hyperactivity but failed to antagonize the reduction of holepokes and rearings. Because 5-HT uptake inhibitors have been found previously to block the MDMA-induced release of 5-HT in vitro, and because fluoxetine was found to have no effect on (+)amphetamine-induced hyperactivity, the present results suggest that (+) MDMA-induced locomotor hyperactivity is dependent on release of endogenous 5-HT. Additionally, prior depletion of central 5-HT with p-chlorophenylalanine partially antagonized the (+)MDMA-induced hyperactivity, although catecholamine synthesis inhibition with alpha-methyl-p-tyrosine did not block the effects of (+)MDMA. Taken together, these studies suggest that (+)MDMA increases locomotor activity via mechanisms that are dependent on the release of central 5-HT and that are qualitatively different from the mechanism of action of (+)amphetamine.