Effect of 3,4-methylenedioxymethamphetamine on [3H]paroxetine binding in the frontal cortex and blood platelets of rats.
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 less than 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 less than 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.
Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106.
J F
JF
Nash
R C
RC
Arora
M A
MA
Schreiber
H Y
HY
Meltzer
D015104:3,4-Methylenedioxyamphetamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007650:Ketanserin / Q000008:administration & dosage; D007700:Kinetics; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D017374:Paroxetine; D010880:Piperidines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
D010880:Piperidines; D012702:Serotonin Antagonists; D014316:Tritium; D012701:Serotonin; D017374:Paroxetine; D015104:3,4-Methylenedioxyamphetamine; D006897:Hydroxyindoleacetic Acid; D007650:Ketanserin; D018817:N-Methyl-3,4-methylenedioxyamphetamine