TY - JOUR
T1 - Age-dependent (+)MDMA-mediated neurotoxicity in mice
AU - Reveron, Maria Elena
AU - Monks, Terrence J.
AU - Duvauchelle, Christine L.
PY - 2005/12/1
Y1 - 2005/12/1
N2 - In the present study the effects of a neurotoxic regimen of (+)-MDMA (20 mg/kg × 4, 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
AB - In the present study the effects of a neurotoxic regimen of (+)-MDMA (20 mg/kg × 4, 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
KW - Dopamine
KW - MDMA
KW - Mice
KW - Microdialysis
KW - Temperature
KW - VMAT2
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UR - http://www.scopus.com/inward/citedby.url?scp=27944480103&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2005.05.006
DO - 10.1016/j.neuro.2005.05.006
M3 - Article
C2 - 15998542
AN - SCOPUS:27944480103
VL - 26
SP - 1031
EP - 1040
JO - NeuroToxicology
JF - NeuroToxicology
SN - 0161-813X
IS - 6
ER -