A neurotoxic regimen of MDMA suppresses behavioral, thermal and neurochemical responses to subsequent MDMA administration.
BACKGROUND
3,4-Methylenedioxymethamphetamine (MDMA) produces a long-term depletion of serotonin (5-HT) in the rat brain; this depletion may have some functional consequences.


OBJECTIVE
The aim of the present study was to evaluate the acute effects of MDMA on the extracellular concentrations of dopamine and 5-HT, body temperature and the 5-HT behavioral syndrome in rats 7 days following a neurotoxic regimen of MDMA.


METHODS
One week after the rats were treated with a neurotoxic regimen of MDMA (10 mg/kg, i.p., every 2 h for a total of four injections), the rats were injected with a subsequent injection of MDMA. In vivo microdialysis combined with HPLC was utilized to measure the extracellular concentration of 5-HT and dopamine in the striatum. The increase in body temperature was determined by rectal temperature measurements, and the 5-HT behavioral syndrome was scored using a rating scale following the administration of MDMA.


RESULTS
The neurotoxic regimen produced a 45% reduction in brain 5-HT concentrations. The magnitude of the MDMA-induced increase in the extracellular concentration of 5-HT, but not dopamine, in the striatum produced by an acute injection of MDMA (7.5 mg/kg, i.p.) was reduced in rats treated previously with the neurotoxic regimen of MDMA when compared with that in control animals. In addition, the magnitude of the 5-HT behavioral syndrome, as well as the hyperthermic response, produced by MDMA was markedly diminished in rats that had previously received the neurotoxic regimen of MDMA.


CONCLUSIONS
It is concluded that the long-term depletion of brain 5-HT produced by MDMA is accompanied by impairments in 5-HT function, as evidenced by the deficits in the neurochemical, thermal and behavioral responses to subsequent MDMA administration.
Shankaran
M
M
College of Pharmacy, University of Cincinnati, OH 45267-0004, USA.
Gudelsky
G A
GA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006213:Hallucinogens / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000523:psychology*; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D020230:Serotonin Syndrome / Q000523:psychology
D006213:Hallucinogens; D009498:Neurotoxins; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine