Behavioural analysis of the acute and chronic effects of MDMA treatment in the rat.
BACKGROUND
A variety of animal models have shown MDMA (3,4-methylenedioxymethamphetamine) to be a selective 5-HT neurotoxin, though little is known of the long-term behavioural effects of the pathophysiology. The widespread recreational use of MDMA thus raises concerns over the long-term functional sequelae in humans.


OBJECTIVE
This study was designed to explore both the acute- and post-treatment consequences of a 3-day neurotoxic exposure to MDMA in the rat, using a variety of behavioural paradigms.


METHODS
Following training to pretreatment performance criteria, animals were treated twice daily with ascending doses of MDMA (10, 15, 20 mg/kg) over 3 days. Body temperature, locomotor activity, skilled paw-reaching ability and performance of the delayed non-match to place (DNMTP) procedure was assessed daily during this period and on an intermittent schedule over the following 16 days. Finally, post mortem biochemical analyses of [3H] citalopram binding and monoamine levels were performed.


RESULTS
During the MDMA treatment period, an acute 5-HT-like syndrome was observed which showed evidence of tolerance. Once drug treatment ceased the syndrome abated completely. During the post-treatment phase, a selective, delay-dependent, deficit in DNMTP performance developed. Post-mortem analysis confirmed reductions in markers of 5-HT function, in cortex, hippocampus and striatum.


CONCLUSIONS
These results confirm that acutely MDMA exposure elicits a classical 5-HT syndrome. In the long-term, exposure results in 5-HT neurotoxicity and a lasting cognitive impairment. These results have significant implications for the prediction that use of MDMA in humans could have deleterious long-term neuropsychological/psychiatric consequences.
Marston
H M
HM
Fujisawa Institute of Neuroscience, Department of Pharmacology, University of Edinburgh, UK. Hugh.Marston@ed.ac.uk
Reid
M E
ME
Lawrence
J A
JA
Olverman
H J
HJ
Butcher
S P
SP
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000378:metabolism; D007700:Kinetics; D008297:Male; D001523:Mental Disorders / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000378:metabolism* / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats
D015306:Biogenic Monoamines; D015283:Citalopram; D018817:N-Methyl-3,4-methylenedioxyamphetamine