Age-dependent (+)MDMA-mediated Neurotoxicity in Mice

Older mice (10-week-old) given a neurotoxic regimen of MDMA showed greater hyperthermia and more severe dopaminergic damage than younger mice (4-week-old). Seven days after treatment, older animals had significant reductions in vesicular monoamine transporter 2 (37%) and tyrosine hydroxylase (58%), while younger animals did not. Dopamine transporter expression dropped in both age groups (26% in younger, 69.7% in older), and striatal dopamine and its metabolite were lower in both, with older animals more affected. The findings indicate age-related susceptibility to MDMA-induced neurotoxicity.

Study at a glance

Abstract

In the present study the effects of a neurotoxic regimen of (+)-MDMA (20 mg/kgx4, s.c.) in 4- and 10-week-old C57Bl/6J mice during treatment and 7 days post-treatment were examined. Rectal temperatures monitored between (+)-MDMA injections (30 min post-injection/2 h intervals) revealed hyperthermic responses in both age groups, with the magnitude of the response significantly greater in older mice. Seven days post-treatment, immunoblot analyses of the vesicular monoamine transporter 2 (VMAT2), and tyrosine hydroxylase (TH) revealed significant reductions (-37 and -58%, respectively) in the older animals, but not in the younger group, compared to age-matched controls. Dopamine transporter (DAT) expression was significantly reduced in both 4- and 10-week-old animals (26 and 69.7%, respectively). (+)-MDMA-treated animals also exhibited significantly lower levels of striatal dopamine, and 3,4-dihydroxyphenylacetic acid than controls, again the effect being more pronounced in the older animals. Although both age groups showed evidence of (+)-MDMA-induced toxicity, our data revealed that older animals exhibited a greater hyperthermic response to (+)-MDMA and were also are more susceptible to subsequent dopaminergic damage than the younger animals.