Altered serotonin innervation patterns in the forebrain of monkeys treatedwith (+/--)3,4-methylenedioxymethamphetamine seven years previously: Factors influencing abnormal recovery

The recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, "Ecstas y") is a potent and selective brain serotonin (5-HT) neurotoxin in animals and, possibly, in humans. The purpose of the present study was to determine whether brain 5-HT deficits persist in squirrel monkeys beyond the 18-mont h period studied previously and to identify factors that influence recovery of injured 5-HT axons. Seven years after treatment, abnormal brain 5-HT in nervation patterns were still evident in MDMA-treated monkeys, although 5-H T deficits in some regions were less severe than those observed at 18 month s. No loss of 5-HT nerve cell bodies in the rostral raphe nuclei was found, indicating that abnormal innervation patterns in MDMA-treated monkeys are not the result of loss of a particular 5-HT nerve cell group. Factors that influence recovery of 5-HT axons after MDMA injury are (1) the distance of the affected axon terminal field from the rostral raphe nuclei, (2) the deg ree of initial 5-HT axonal injury, and possibly (3) the proximity of damage d 5-HT axons to myelinated fiber tracts. Additional studies are needed to b etter understand these and other factors that influence the response of pri mate 5-HT neurons to MDMA injury and to determine whether the present findi ngs generalize to humans who use MDMA for recreational purposes.