Age-dependent (+)MDMA-mediated Neurotoxicity in Mice
María E. Reverón, Terrence J. Monks, Christine L. Duvauchelle
Neurotoxicology July 6, 2005 DOI: 10.1016/j.neuro.2005.05.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | 4- and 10-week-old C57Bl/6J mice |
| Intervention | (+)-MDMA |
| Dose | 20 mg/kgx4, s.c. |
| Duration | 7 days post-treatment |
| Topics | MDMA Serotonin |
| Keywords | Dopaminergic Dopamine transporter Monoamine neurotransmitter Neurotoxicity Vesicular monoamine transporter Tyrosine hydroxylase Endocrinology Striatum Pharmacology |
| Citations | 24 |
| Key findings | Older mice exhibited greater hyperthermic response to MDMA and were more susceptible to subsequent dopaminergic damage than younger mice. |
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.