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.
BACKGROUND
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, 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.


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.
Balogh
Brigitta
B
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.
Molnar
Eszter
E
Jakus
Rita
R
Quate
Linda
L
Olverman
Henry J
HJ
Kelly
Paul A T
PA
Kantor
Sandor
S
Bagdy
Gyorgy
G
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D012890:Sleep / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects
D005947:Glucose; D018817:N-Methyl-3,4-methylenedioxyamphetamine