A neurotoxic regimen of MDMA suppresses behavioral, thermal and neurochemical responses to subsequent MDMA administration

• Published in: Psychopharmacologia Vol. 147; no. 1; pp. 66 - 72
• Main Authors: SHANKARAN, Mahalakshmi, GUDELSKY, Gary A
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.11.1999
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Body Temperature - drug effects; Brain Chemistry - drug effects; Dopamine - metabolism; Dose-Response Relationship, Drug; Drug addictions; Extracellular Space - drug effects; Extracellular Space - metabolism; Hallucinogens - administration & dosage; Hallucinogens - toxicity; Injections, Intraperitoneal; Male; Medical sciences; Microdialysis; N-Methyl-3,4-methylenedioxyamphetamine - administration & dosage; N-Methyl-3,4-methylenedioxyamphetamine - toxicity; Neurotoxicity Syndromes - psychology; Neurotoxins - administration & dosage; Neurotoxins - toxicity; Rats; Rats, Sprague-Dawley; Serotonin - metabolism; Serotonin Syndrome - psychology; Toxicology; Intraperitoneal administration; Rat; Toxicity; Central nervous system; Posture; Dose activity relation; Behavioral disorder; Multiple dose; Drug of abuse; Mechanism of action; Drug addiction; Nervous system diseases; Dopamine; Serotonin; Illicit drug; Body temperature; Rodentia; Corpus striatum; Catecholamine; Long term; Cerebral disorder; Vertebrata; Mammalia; Serotoninergic pathway; Animal; Central nervous system disease; Brain (vertebrata)
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130051143

3,4-Methylenedioxymethamphetamine (MDMA) produces a long-term depletion of serotonin (5-HT) in the rat brain; this depletion may have some functional consequences. 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. 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. 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. 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.