METHYLENEDIOXYMETHAMPHETAMINE-INDUCED SEROTONIN DEFICITS ARE FOLLOWEDBY PARTIAL RECOVERY OVER A 52-WEEK PERIOD .1. SYNAPTOSOMAL UPTAKE ANDTISSUE CONCENTRATIONS

The effects of a high dose methylenedioxymethamphetamine (MDMA) regime n on the serotonin (5-HT) system were evaluated over a 52-wk period. M DMA was administered to rats (20 mg/kg) 8 times at 12-hr intervals. Ti ssue concentrations of dopamine (DA) and 5-HT, and synaptosomal uptake of H-3-5-HT and H-3-DA were measured at 2, 8, 16, 32 or 52 wk posttre atment. 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 concent rations were measured in frontal cortex, frontal-parietal cortex, occi pital-temporal cortex, nucleus accumbens/olfactory tubercle, striatum, amygdala, hippocampus, septum, hypothalamus, ventral tegmentum/substa ntianigra. Two weeks after MDMA treatment, all regions showed decrease d 5-HT tissue concentrations except septum. Recovery over the 52-wk in terval was noted for all depleted regions, but the rate and degree of recovery was region dependent. Frontal-parietal cortex, occipital-temp oral cortex and hippocampus showed the least recovery, with significan t depletions at 52 wk posttreatment. Hypothalamus showed an increase i n 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 s erotonin tissue concentrations seen over the 52-wk test period is regi on specific.