3,4-Methylenedioxymethamphetamine-induced release of serotonin and inhibition of dorsal raphe cell firing: potentiation by L-tryptophan.
The effects of the serotonin (5-HT) precursor L-tryptophan on MDMA (3,4-methylenedioxymethamphetamine)-induced inhibition of dorsal raphe neuronal firing were characterized using extracellular single-unit recording and microdialysis techniques in the in vitro midbrain slice preparation. Pretreatment with L-tryptophan (100 microM) lowered the doses of MDMA required to inhibit unit activity. Based upon IC50 values, L-tryptophan increased the potency of MDMA by approximately 3-fold. In a parallel series of experiments, microdialysis probes resting on the brain slice surface provided a means to estimate 5-HT release from the dorsal raphe nucleus. Pretreatment with L-tryptophan increased MDMA-induced 5-HT release in a manner consistent with the suppression of dorsal raphe cell firing: compared to untreated preparations, peak 5-HT release, total release and the duration of release were all increased. Taken together, these data suggest that the enhancement by L-tryptophan of MDMA-induced 5-HT release and inhibition of dorsal raphe neuronal firing is due to an increase in the amount of 5-HT available for release. The question is raised as to what effect L-tryptophan may have on the psychotropic and neurotoxic actions of MDMA.
Sprouse
J S
JS
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508.
Bradberry
C W
CW
Roth
R H
RH
Aghajanian
G K
GK
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000494:pharmacology*
D000662:Amphetamines; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D014364:Tryptophan; D018817:N-Methyl-3,4-methylenedioxyamphetamine