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 le vels 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. N either 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 affecte d in the cerebellar cortex and hippocampus after either a single or mu ltiple injections of METH. In a second set of experiments, an intraper itoneal injection of 2-deoxyglucose (2-DG; 1 g/kg), an inhibitor of gl ucose uptake and utilization, was given 30 min before the third and fo urth injections of METH. 2-DG significantly potentiated METH-induced s triatal 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 cause s striatal energy impairment and raise the possibility that perturbati ons of energy metabolism play a role in METH-induced dopaminergic neur otoxicity.