Effects of a single dose of 3,4-methylenedioxymethamphetamine on circadian patterns, motor activity and sleep in drug-naive rats and rats previously exposed to MDMA

Rationale Despite the well documented neurochemical actions of 3,4-methylenedioxymethamphetamine (MDMA), acute effects in rats previously exposed to the drug have not been extensively explored.Objective To examine motor activity and vigilance effects of MDMA in drug-naive rats and in rats exposed to the drug 3 weeks earlier.Methods MDMA (15 mg/kg, IP) was administered to Dark Agouti rats. Motor activity, wakefulness, light slow wave sleep (SWS-1), deep slow wave sleep (SWS-2) and paradoxical sleep (PS), sleep and PS latencies were measured. Acrophases and amplitudes of the 24 h cycles were calculated by cosinor analysis. In parallel groups, local cerebral glucose utilization (lCMR_glu) and (³H)-paroxetine binding were measured in motor areas of the brain.Results In drug-naive rats MDMA caused marked increases in motor activity and wakefulness for at least 5–6 h. Circadian patterns of motor activity and sleep/vigilance parameters were altered up to 5 days after treatment. Despite most parameters tending to return to normal, there were still significant effects of MDMA on motor activity, wakefulness, and SWS-2 28 days later. Acute MDMA administration caused significant increases in lCMR_glu, but after 3 weeks lCMR_glu was decreased in the same brain areas. No significant change in [³H]paroxetine binding was observed in motor areas, although significant reductions were seen elsewhere (neocortex –81%). In rats exposed to MDMA 3 weeks earlier, most acute effects induced by MDMA administration were similar to those in drug-naive rats, but shorter duration of the acute effects were found in motor activity and vigilance.Conclusions Our findings provide evidence that MDMA use can lead to long-term changes in regulation of circadian rhythms, motor activity and sleep generation.