Neurotoxicity of amphetamines and their metabolites.

When amphetamine or an analog is administered in repeated high doses, neurochemical deficits in both the dopaminergic and serotonergic systems of selected areas of the brain are observed. Methamphetamine (10 to 15 milligrams per kilogram (mg/kg)), administered every 6 hours for 5 doses, decreases rat tyrosine hydroxylase (TH) activity and dopamine (DA) content in the neostriatum within 18 hours after the first dose (Koda and Gibb 1973). Interestingly, these neurochemical deficits persist in rats and nonhuman primates for extended periods of time after the drug is discontinued (Ellison et al. 1978; Bakhit et al. 1981; Woolverton et al. 1989).