The acute and long-term neurotoxic effects of MDMA on marble burying behaviour in mice.
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 micro 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.
Saadat
Kathryn S
KS
Neuropharmacology Research Group, Leicester School of Pharmacy, De Montfort University, UK.
Elliott
J Martin
JM
Colado
M Isabel
MI
Green
A Richard
AR
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D006213:Hallucinogens / Q000633:toxicity*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D011619:Psychotropic Drugs / Q000633:toxicity; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000633:toxicity*; D013239:Stereotyped Behavior / Q000187:drug effects*; D010133:p-Chloroamphetamine / Q000633:toxicity
D006213:Hallucinogens; D011619:Psychotropic Drugs; D018490:Serotonin Agents; D012701:Serotonin; D010133:p-Chloroamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine