This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human MDMA users display selective cognitive deficits, acutely or following repeated exposure to MDMA. We compared the duration of oral or i.m. MDMA on higher executive function in primates and, based on our in vitro data, the efficacy of e norepinephrine (NET), serotonin (SERT) or dopamine (DAT) transport inhibitors to alleviate impairment. Adult cynomolgus monkeys (Macaca fasicularis) were trained to stable performance in a cognitive task. The effects of once-weekly oral or i.m. MDMA (1.5 mg/kg, n = 4) on performance was monitored, alone or after pretreatment with inhibitors of the SERT (citalopram), DAT (methylphenidate), or NET (desipramine). Results: Oral MDMA increased error rates in a cognitive task on the day of, and for 2 days after exposure but intramuscular MDMA eliminated task performance on the day of administration. Impairment dissipated rapidly, and resurfaced sporadically. Citalopram or desipramine antagonism of MDMA-mediated deficits were associated with their potencies to block [3H]monoamines, but not (3H)MDMA transport. MDMA altered sleep latency. Discussion: The findings implicate the NET and noradrenergic activity in MDMA effects and warrant investigation of the therapeutic potential of NET inhibitors for MDMA-induced cognitive impairment.
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