Effect of 3,4-methylenedioxymethamphetamine on [3H]paroxetine binding in the frontal cortex and blood platelets of rats

J. Frank Nash*, Ramesh C. Arora, Matthew A. Schreiber, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The effects of single or repeated administration of the racemic mixture of 3,4-methylenedioxymethamphetamine (MDMA; 20 mg/kg, s.c.) on the number (Bmax) of serotonin (5-HT) uptake sites as determined by [3H]paroxetine binding and the concentration of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were measured in the frontal cortex and blood platelets of rats 1 and 7 days following its administration. A single injection of MDMA significantly (P < 0.05) decreased the number of [3H]paroxetine binding sites as well as the concentrations of 5-HT and 5-HIAA in the frontal cortex but not in platelets 7 days following administration. Repeated injections of MDMA (twice daily for 4 days) significantly (P < 0.05) decreased the number of 5-HT uptake sites and the concentration of 5-HT and 5-HIAA in the frontal cortex but not in platelets 7 days following administration. Pretreatment with the 5-HT2/5-HT1C antagonist, ketanserin, inhibited the MDMA-induced decrease in 5-HT and 5-HIAA concentrations and the number of [3H]paroxetine binding sites in the frontal cortex 7 days following a single administration. These data are suggestive that blood platelets are less sensitive than brain tissue to the 5-HT-depleting effects of MDMA. The ability of ketanserin pretreatment to block MDMA-induced decreases in [3H]paroxetine binding sites in the frontal cortex is suggestive that 5-HT2/5-HT1C receptors may be involved in the neurotoxic effects of MDMA.

Original languageEnglish (US)
Pages (from-to)79-84
Number of pages6
JournalBiochemical Pharmacology
Volume41
Issue number1
DOIs
StatePublished - Jan 1 1991

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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