Age-dependent (+)MDMA-mediated neurotoxicity in mice.
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.
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, TX 78712, USA.
Maria Elena
ME
Reveron
Terrence J
TJ
Monks
Christine L
CL
Duvauchelle
D000375:Aging / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005334:Fever / Q000139:chemically induced*; D006213:Hallucinogens / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000378:metabolism / Q000633:toxicity*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D006213:Hallucinogens; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; D014446:Tyrosine 3-Monooxygenase; D018817:N-Methyl-3,4-methylenedioxyamphetamine