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Serotonin release contributes to the locomotor stimulant effects of 3,4-methylenedioxymethamphetamine in rats.
J Pharmacol Exp Ther. 1990 Aug; 254(2):456-64.JP

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.

Authors+Show Affiliations

Department of Psychiatry, UCSD School of Medicine, La Jolla.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1974635

Citation

Callaway, C W., et al. "Serotonin Release Contributes to the Locomotor Stimulant Effects of 3,4-methylenedioxymethamphetamine in Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 254, no. 2, 1990, pp. 456-64.
Callaway CW, Wing LL, Geyer MA. Serotonin release contributes to the locomotor stimulant effects of 3,4-methylenedioxymethamphetamine in rats. J Pharmacol Exp Ther. 1990;254(2):456-64.
Callaway, C. W., Wing, L. L., & Geyer, M. A. (1990). Serotonin release contributes to the locomotor stimulant effects of 3,4-methylenedioxymethamphetamine in rats. The Journal of Pharmacology and Experimental Therapeutics, 254(2), 456-64.
Callaway CW, Wing LL, Geyer MA. Serotonin Release Contributes to the Locomotor Stimulant Effects of 3,4-methylenedioxymethamphetamine in Rats. J Pharmacol Exp Ther. 1990;254(2):456-64. PubMed PMID: 1974635.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serotonin release contributes to the locomotor stimulant effects of 3,4-methylenedioxymethamphetamine in rats. AU - Callaway,C W, AU - Wing,L L, AU - Geyer,M A, PY - 1990/8/1/pubmed PY - 1990/8/1/medline PY - 1990/8/1/entrez SP - 456 EP - 64 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 254 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/1974635/Serotonin_release_contributes_to_the_locomotor_stimulant_effects_of_34_methylenedioxymethamphetamine_in_rats_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1974635 DB - PRIME DP - Unbound Medicine ER -