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
Balogh B, Molnar E, Jakus R, Quate L,
Olverman HJ, Kelly PA, Kantor S, Bagdy G.
Laboratory of Neurochemistry and Experimental Medicine
and Department of Vascular Neurology, Semmelweis University,
National Institute of Psychiatry and Neurology,
Huvosvolgyi ut 116, 1021, Budapest, Hungary.
Psychopharmacology (Berl). 2004 Apr 9


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 ((3)H)-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 [(3)H]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.

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