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

The drug MDMA (Ecstasy) damages dopamine nerve terminals in the mouse striatum, with a greater effect in striosomes—specialized brain compartments linked to different functions—than in the surrounding matrix. Mice given MDMA showed significant reductions in two markers of dopamine neurons, tyrosine hydroxylase and dopamine transporter, compared with controls. The loss was considerably more pronounced in striosomes, indicating that these compartments are more vulnerable to MDMA's long-term neurotoxicity. This provides the first evidence that striosome and matrix compartments differ in their sensitivity to MDMA, with the damage primarily involving striosomal dopamine fibers.

Study at a glance

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.