Early loss of dopaminergic terminals in striosomes after MDMA administration to mice

Summary

MDMA, commonly known as Ecstasy, significantly impacts the brain's striatum, particularly affecting dopamine levels. In a study involving mice, those treated with MDMA exhibited a 40% reduction in tyrosine hydroxylase and dopamine transporter immunostaining in the striatum compared to controls. Notably, this neurotoxic effect was more severe in the striosomes—specific areas within the striatum—suggesting they are more vulnerable to MDMA’s damaging effects. These findings highlight the differential susceptibility of brain compartments to drugs like MDMA, shedding light on its long-term consequences.

Abstract

Abstract The amphetamine analogue 3,4‐methylenedioxymethamphetamine (MDMA or “Ecstasy”) is a popular drug of abuse which causes different neurotoxic effects in the mouse compared with the rat. In mice, MDMA produces damage to striatal dopamine terminals, having little long‐term effects on serotonin (5‐HT) containing neurons. A relevant feature of the striatum is its striosome/matrix compartmental organization; defined by different connexions, and functions. In this study we examined the long‐term effect induced by MDMA on tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoreactivity in the striosomes and matrix compartments of mouse striatum. Mice given MDMA showed significant reductions in TH and DAT immunostaining in striatum compared with control animals. Interestingly, this effect was considerably more pronounced in striosomes than in the matrix. These data provide the first evidence that striosomes and matrix compartments of the mouse striatum have differential vulnerability to MDMA and that the long‐term neurotoxicity induced by MDMA in mice is primarily associated with a loss of striosomal dopamine fibres. Synapse 62:80–84, 2008. © 2007 Wiley‐Liss, Inc.

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