Biphasic effects of selegiline on striatal dopamine: Lack of effect on methamphetamine-induced dopamine depletion

We tested the hypothesis that selegiline can attenuate dopamine depletion i f administered following high doses of methamphetamine that cause neurotoxi city in the striatum. Methamphetamine produced decreases of 50% or greater in both striatal concentrations of dopamine and combined concentrations of homovanillic acid and DOPAC in mice. For animals not exposed to methampheta mine, chronic treatment with selegiline over 18 days caused biphasic effect s on striatal dopamine content, with decreases, no effect, or increases obs erved for mice receiving treatment with 0.02, 0.2, and 2.0 mg/kg, respectiv ely. Selegiline failed to modify methamphetamine-induced reductions in stri atal dopamine content or combined concentrations of homovanillic acid and D OPAC. Significant increases in mortality following the onset of selegiline treatment (24 hours after the initial dose of methamphetamine) occurred in methamphetamine-treated mice that received saline or 2.0 mg/kg of selegilin e, but not for mice treated with 0.02 or 0.2 mg/kg of selegiline, These res ults indicate that selegiline fails to attenuate dopamine depletion when ad ministered chronically following exposure to methamphetamine, but may atten uate methamphetamine-induced mortality. In control animals that did not rec eive methamphetamine, low doses of selegiline produced decreases the concen tration of striatal dopamine, while high dose treatment caused increases in striatal dopamine content.