Striatal postsynaptic ultrastructural alterations following methylenedioxymethamphetamine administration

Abstract

Amphetamine derivatives, such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA), act as monoaminergic neurotoxins in the central nervous system. Although there are slight differences in their mechanism of action, these compounds share a final common pathway, which involves dopamine release and oxidative stress. Apart from striatal toxicity involving monoamine axons, no previous report evidenced any alteration at the striatal level concerning postsynaptic sites. Given the potential toxicity for extracellular dopamine at the striatal level, and the hypothesis for neurotoxic effects of dopamine on striatal medium-sized neurons in Huntington's disease, we evaluated at an ultrastructural level the effects of MDMA on intrinsic striatal neurons of the mouse. In this study, administering MDMA, we noted ultrastructural alterations of striatal postsynaptic GABAergic cells consisting of neuronal inclusions shaped as whorls of concentric membranes. These whorls stained for ubiquitin but not for synuclein and represent the first morphologic correlate of striatal postsynaptic effects induced by MDMA.