Abstract
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 (lCMRglu) 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 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.
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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Acknowledgements
This study was supported by the Fifth Framework Programme of the European Community, QLG3-CT-2002-00809, the Hungarian Research Fund Grant T020500 and M27976, the Ministry of Welfare Research Grant 058/2003 and the Fund Management of Ministry of Education OMFB 01926/2002. The experiments complied with the Hungarian Governmental Regulation about animal studies (presented December 31, 1998) and the United Kingdom Animals Act (1986). We thank Professor Franz Halberg and Dr. Germaine Cornelissen (Chronobiology Laboratories, University of Minnesota, Minneapolis, Minn., USA) for their expert advice regarding parameters of circadian activity.
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Balogh, B., Molnar, E., Jakus, R. et al. 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. Psychopharmacology 173, 296–309 (2004). https://doi.org/10.1007/s00213-004-1787-9
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DOI: https://doi.org/10.1007/s00213-004-1787-9