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

• Published in: Psychopharmacology 2004-05, Vol.173 (3-4), p.296-309
• Main Authors: Balogh, Brigitta, Molnar, Eszter, Jakus, Rita, Quate, Linda, Olverman, Henry J, Kelly, Paul A T, Kantor, Sandor, Bagdy, Gyorgy
• Format: Article
• Language: English
• Subjects: Animals; Autoradiography; Brain - drug effects; Brain - metabolism; Circadian rhythm; Circadian Rhythm - drug effects; Drug dosages; Ecstasy; Glucose - metabolism; Laboratory animals; Male; Motor Activity - drug effects; N-Methyl-3,4-methylenedioxyamphetamine - administration & dosage; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology; Pacemakers; Radioligand Assay; Rats; Serotonin; Sleep; Sleep - drug effects; Wakefulness - drug effects
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-004-1787-9

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. To examine motor activity and vigilance effects of MDMA in drug-naive rats and in rats exposed to the drug 3 weeks earlier. MDMA (15 mg/kg, i.p.) 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 (lCMRglu) and (3H)-paroxetine binding were measured in motor areas of the brain. 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 lCMRglu, but after 3 weeks lCMRglu 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. Our findings provide evidence that MDMA use can lead to long-term changes in regulation of circadian rhythms, motor activity and sleep generation.