MDMA (3,4-Methylenedioxymethamphetamine) is a drug of abuse that is gaining notoriety for its use in large organized social gatherings (""""""""raves""""""""). MDMA is also a potent and selective neurotoxicant to the serotonergic neurotransmitter system. The primary focus of this proposal is to investigate the potential of developmental exposure to MDMA for producing alterations in learning and memory.
The specific aims of this proposal are to determine if developmental MDMA exposures (1) alter paradigms of learning and memory, and (2) alter measures of sensorimotor reactivity.
These aims will be accomplished by administering MDMA to rats during two neonatal periods of development (postnatal days 1-10 or 11-20). Acoustic startle reactivity and performance in the Morris water maze will be assessed when the rats reach adulthood. Upon completion of behavioral testing, rats will be evaluated for chronic alterations in neurochemical indices of serotonergic function. This will determine if repeated MDMA administration to neonates produces serotonergic deficits lasting into adulthood. A group of adult rats will be treated with MDMA to compare the differences between adult and developmental exposures of this compound. MDMA will be administered for 10 days to adult rats as in the neonatal rats. Ten days after MDMA treatment, these adult rats will be tested for acoustic startle reactivity and performance in the Morris water maze. After completion of the behavioral testing, these adult rats will be sacrificed for neurochemical evaluation to determine the extent of MDMA- induced serotonergic neurotoxicity. These experiments will test the hypothesis that developmental exposure to MDMA will elicit irreversible behavioral deficits. Specifically, developmental exposures of MDMA will (1) produce deficits in tests of learning and memory, (2) produce alterations in tests of sensorimotor reactivity, (3) produce alterations that vary with the developmental stage at which MDMA is administered, and (4) produce alterations that are dependent on dose.
