Methylenedioxyamphetamine: a selective effect on cortical content and turnover of 5-HT.

This study examined the effects of the hallucinogen, MDA, on brain content of monoamines and their metabolites in the rabbit. A single 1.8 mg/kg dose of MDA produced 30 to 64% increases in the 5-HT content of frontal cortex from 30 to 120 min after injection and a decrease in 5-HT turnover from 30 min to 8 h, but had no effect in hippocampus, caudate nucleus, or hypothalamus. A single 3.6 mg/kg dose of MDA also reduced the turnover of 5-HT in frontal cortex, but this was accompanied by a decrease in 5-HIAA with no increase in 5-HT. The 1.8 and 3.6 mg/kg doses of MDA had no significant or consistent effects on the contents of DA, DOPAC, HVA, and NE in any brain area examined. Chronic administration of MDA (3.6 mg/kg/day for 4 days) failed to produce any evidence of a neurotoxic action on 5-HT neurons. Higher doses could not be employed because the LD50 of MDA was approximately 5 mg/kg. This study has demonstrated that behaviorally effective and nonneurotoxic doses of MDA produce increases in the content and decreases in turnover of 5-HT in frontal cortex that resemble those of other hallucinogens such as LSD and DOM.