Effect of methamphetamine on norepinephrine metabolism in various regions of brain.

The effects of methamphetamine on tritiated and endogenous norepinephrine metabolism was examined in various regions of brain. In acute experiments, 30 minutes or 5 hours after methamphetamine i.p., 3H-norepinephrine was injected into the cisterna magna. In chronic experiments, rats were administered increasing doses of methamphetamine twice a day for 17 days, then 18 hours after the last dose of methamphetamine, 3H-norepinephrine was injected intracisternally. All rats were killed 5 minutes after the intracisternal injection and their brains removed, dissected into five parts and assayed for endogenous norepinephrine, 3H-norepinephrine and its metabolites. In rats treated acutely, methamphetamine caused a significant block in uptake of 3H-norepinephrine and a marked increase in the content of 3H-normetanephrine in all regions except the cortex. Five hours after methamphetamine administration, increased levels of 3H-norepinephrine occurred in the pons-medulla, whereas endogenous norepinephrine content tended to decrease in most regions. In rats treated chronically, enhanced accumulation of 3H-norepinephrine was also confined to the pons-medulla region, whereas endogenous levels of norepinephrine were high in the pons-medulla and low in the hypothalamus and cortex. These data suggest that chronic administration of methamphetamine affects either catecholaminergic nerve cell bodies or nerve terminals in the pons-medulla differentially, as compared to other regions studied.