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The acute and long-term neurotoxic effects of MDMA on marble burying behaviour in mice

J. Martin Elliott

Neuropharmacology Research Group, Leicester School of Pharmacy, De Montfort University, Leicester, UK

M. Isabel Colado

Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain

A. Richard Green

AstraZeneca R&D Charnwood, Loughborough, UK

When mice are exposed to harmless objects such as marbles in their cage they bury them, a behaviour sometimes known as defensive burying. We investigated the effect of an acute dose of MDMA (èecstasy') and other psychoactive drugs on marble burying and also examined the effect of a prior neurotoxic dose of MDMA or p-chloroamphetamine (PCA) on burying. Acute administration of MDMA produced dose-dependent inhibition of marble burying (EC50: 7.6 µ mol/kg). Other drugs that enhance monoamine function also produced dose-dependent inhibition: methamphetamine PCA paroxetine MDMA GBR 12909 methylphenidate. None of these drugs altered locomotor activity at a dose that inhibited burying. A prior neurotoxic dose of MDMA, which decreased striatal dopamine content by 60%, but left striatal 5-HT content unaltered, did not alter spontaneous marble burying 18 or 40 days later. However, a neurotoxic dose of PCA which decreased striatal dopamine by 60% and striatal 5-HT by 70% attenuated marble burying 28 days later. Overall, these data suggest that MDMA, primarily by acutely increasing 5-HT function, acts like several anxiolytic drugs in this behavioural model. Long-term loss of cerebral 5-HT content also produced a similar effect. Since this change was observed only after 28 days, it is probably due to an adaptive response in the brain.

Key Words: 5-HT • amphetamines • anxiety • defensive burying • dopamine • ecstasy • marbles • MDMA • p-chloroamphetamine

Journal of Psychopharmacology, Vol. 20, No. 2, 264-271 (2006)
DOI: 10.1177/0269881106058022


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