METHYLPHENIDATE AND BRAIN DOPAMINE NEUROTOXICITY

To further evaluate the dopamine (DA) neurotoxic potential of the wide ly prescribed psychostimulant, methylphenidate, mice were treated with various doses (range: 10-120 mg/kg) and treatment schedules of methyl phenidate (every 2 h X 4 or twice daily X 4). Higher doses of methylph enidate produced intense stereotypy, as well as short- (5-day), but no t long- (2-week), term depletions of striatal DA axonal markers. By co ntrast, amphetamine caused not only intense stereotypy, but also profo und, long-lasting, dose-related DA deficits. These findings indicate t hat results of studies of amphetamine neurotoxicity using short (5-day ) post-drug survival periods are potentially misleading. Further, the present findings confirm and extend previous results indicating that m ethylphenidate, unlike amphetamine, lacks DA neurotoxic potential, and strongly suggest that DA efflux, although perhaps necessary, is not s ufficient for the expression of amphetamine-induced DA neurotoxicity. (C) 1997 Elsevier Science B.V.