Lack of serotonin neurotoxicity after intraraphe
microinjection of (+)-3,4-methylenedioxymethamphetamine (MDMA)

Paris JM, Cunningham KA.
Department of Pharmacology and Toxicology,
University of Texas Medical Branch, Galveston 77550.
Brain Res Bull1992 Jan;28(1):115-9


Systemic administration of 3,4-methylenedioxymethamphetamine (MDMA) produces depletions of serotonin (5-HT) and its primary metabolite, 5-hydroxyindoleacetic acid (5-HIAA), decreases 5-HT reuptake sites and diminishes tryptophan hydroxylase activity in various forebrain regions. MDMA has been shown to be neurotoxic to the fine fibers originating from dorsal raphe (DR) 5-HT neurons but not the beaded fibers from the median raphe (MR) nucleus. In the present experiment, MDMA was microinjected directly into the DR or MR to determine whether differential neurotoxicity developed in the DR versus MR fiber systems as measured by 5-HT levels and immunocytochemistry. Two weeks following stereotaxic injection with either vehicle or (+)MDMA (50 micrograms base in 2 microliters) into the DR or MR, rat brains were assayed for 5-HT and catecholamine content or 5-HT immunocytochemistry. HPLC analysis revealed no significant changes in monoamine or metabolite concentrations in the hippocampus and striatum of rats administered intra-DR or -MR (+)MDMA. Raphe sections stained for 5-HT also did not reveal any apparent neurotoxicity. A single cerebral injection of (+)MDMA does not produce neurotoxicity to 5-HT neuronal systems originating in the raphe, although neurotoxicity of multiple MDMA injections into these raphe nuclei cannot be ruled out.

Parkinsonian primates?
Long-term brain damage?
Toxic metabolites of MDMA?
MDMA and sympathetic activity
A toxic intraneuronal metabolite of serotonin?
Electrophysiological evidence of 5-HT damage
Non-neurotoxic and neurotoxic serotonin-releasers
Ecstasy-induced toxicity and the dopamine transporter
5-HT, 5-HIAA, norepinephrine, epinephrine and dopamine

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