Recreational use of (+/-) 3,4 -methylenedioxymethamphetamine (MDMA, """"""""Ecstasy"""""""") has become increasingly popular in recent decades. Major surveys in the US report steep increases in the rate of MDMA use while use of a number of other recreational drugs has been stable or in decline. College age adults have lifetime prevalence rates of 12-18% thus a substantial fraction of the population is exposed to MDMA. Numerous studies have shown that abstinent MDMA users exhibit deficits on a range of cognitive tasks. Work in nonhuman primate models over past decades has shown that high doses of MDMA (10 mg/kg);when administered at 12 hr intervals for 4 days, selectively reduce markers for serotonin (5-HT) axons and terminals in many brain regions. However, such MDMA-associated 5-HT neurotoxicity is not sufficient to produce cognitive or motor alterations in monkeys under unchallenged conditions. Prior monkey models have not employed repeated, intermittent dosing patterns similar to human users, however. To investigate the novel hypothesis that cognitive and motor disturbances in human users of MDMA result from repeated cycles of 5HT axon pruning/reinnervation, experiments will be conducted in rhesus macaques under the following Aims.
Specific Aim I : To determine if repeated, intermittent exposure to a low dose of MDMA results in detectable neurochemical, behavioral or electrophysiological alterations.
Specific Aim II : To determine if a short-interval, multi-dose exposure to low doses of MDMA (""""""""MDMA stacking"""""""") results in a neurochemical, behavioral and electrophysiological profile similar to that produced by the repeated, high-dose, long interval regimen that produces serotonin neurotoxicity.
Specific Aim III : To determine if repeated episodes of exposure to MDMA result in progressive electrophysiological, neurochemical or chronophysiological disturbance.
Specific Aim I V: To determine if a history of MDMA exposure impairs acquisition and performance of a battery of neuropsychological tests.
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