Rapid ATP loss caused by methamphetamine in the mouse striatum: relationship between energy impairment and dopaminergic neurotoxicity.
To study the relationship between energy impairment and the effects of d-methamphetamine (METH) on dopaminergic neurons, ATP and dopamine levels were measured in the brain of C57BL/6 mice treated with either a single or four injections of METH (10 mg/kg, i.p.) at 2-h intervals. Neither striatal ATP nor dopamine concentrations changed after a single injection of METH, but both were significantly decreased 1.5 h after the multiple-dose regimen. The effects of METH on ATP levels appear to be selective for the striatum, as ATP concentrations were not affected in the cerebellar cortex and hippocampus after either a single or multiple injections of METH. In a second set of experiments, an intraperitoneal injection of 2-deoxyglucose (2-DG; 1 g/kg), an inhibitor of glucose uptake and utilization, was given 30 min before the third and fourth injections of METH. 2-DG significantly potentiated METH-induced striatal ATP loss at 1.5 h and dopamine depletions at 1.5 h and 1 week. These results indicate that a toxic regimen of METH selectively causes striatal energy impairment and raise the possibility that perturbations of energy metabolism play a role in METH-induced dopaminergic neurotoxicity.
Chan
P
P
Parkinson's Institute, Sunnyvale, CA 94089.
Di Monte
D A
DA
Luo
J J
JJ
DeLanney
L E
LE
Irwin
I
I
Langston
J W
JW
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003847:Deoxyglucose / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*
D009498:Neurotoxins; D008694:Methamphetamine; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D004298:Dopamine