No effect of MDMA (ecstasy) on cell death and 5-HT2A receptor density in organotypic rat hippocampal cultures.
MDMA (3,4 Methylenedioxy-methamphetamine) binds and blocks the presynaptic serotonin reuptake transporters and postsynaptic serotonin 5-HT2A receptors, with highest affinity for the first. Whether 5-HT2A receptor density decreases due to MDMA's direct effect on postsynaptic serotonin receptors is at present not known. This study analyzes whether direct stimulation of the postsynaptic 5-HT2A receptor by MDMA in organotypic hippocampal cultures results in cell death and downregulation of this receptor. Fifty or 100 microM MDMA was added to 1 week old cultures, made of 11 day old rat pups. Fluorojade and immunostaining for MAP2 and 5-HT2A to determine neurodegeneration, and changes in receptor density, respectively, resulted in no significant differences. MDMA's neurotoxicity and regulation of post-synaptic 5-HT2A receptors thus seems to require the presence of intact serotonergic terminals.
Sveen
Marie-Louise
ML
Neurobiology Research Unit, Copenhagen University Hospital, Unit 9201, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Knudsen
Gitte M
GM
Aznar
Susana
S
D000818:Animals; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000032:analysis* / Q000378:metabolism
D044402:Receptor, Serotonin, 5-HT2A; D018817:N-Methyl-3,4-methylenedioxyamphetamine