title: Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 52-week period. Part I: Synaptosomal uptake and tissue concentrations.
abstract: The effects of a high dose methylenedioxymethamphetamine (MDMA) regimen on the serotonin (5-HT) system were evaluated over a 52-wk period. MDMA was administered to rats (20 mg/kg) 8 times at 12-hr intervals. Tissue concentrations of dopamine (DA) and 5-HT, and synaptosomal uptake of 3H-5-HT and 3H-DA were measured at 2, 8, 16, 32 or 52 wk posttreatment. Synaptosomal uptake of 3H-5-HT (hippocampus) was decreased at 2 and 8 wk, but not at 16, 32 or 52 wk after drug. 5-HT tissue concentrations were measured in frontal cortex, frontal-parietal cortex, occipital-temporal cortex, nucleus accumbens/olfactory tubercle, striatum, amygdala, hippocampus, septum, hypothalamus, ventral tegmentum/substantia nigra. Two weeks after MDMA treatment, all regions showed decreased 5-HT tissue concentrations except septum. Recovery over the 52-wk interval was noted for all depleted regions, but the rate and degree of recovery was region dependent. Frontal-parietal cortex, occipital-temporal cortex and hippocampus showed the least recovery, with significant depletions at 52 wk posttreatment. Hypothalamus showed an increase in 5-HT tissue concentrations relative to age-matched controls at 52 wk. These results indicate that a high-dose MDMA regimen results in long-lasting depletions of serotonin. The rate and degree of recovery of serotonin tissue concentrations seen over the 52-wk test period is region specific.
authors.affiliation: University of Chicago, Department of Pharmacological and Physiological Sciences, Illinois, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Sabol
authors.forename: R
authors.initials: R
authors.lastname: Lew
authors.forename: J B
authors.initials: JB
authors.lastname: Richards
authors.forename: G L
authors.initials: GL
authors.lastname: Vosmer
authors.forename: L S
authors.initials: LS
authors.lastname: Seiden
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D018490:Serotonin Agents / Q000633:toxicity*; D013574:Synaptosomes / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018490:Serotonin Agents; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine