Methamphetamine-induced striatal apoptosis in the mouse brain: comparison of a binge to an acute bolus drug administration.

Methamphetamine (METH) is a psychostimulant that induces neural damage in experimental animals and humans. A binge (usually in the 5-10 mg/kg dose range 4 x at 2 h intervals) and the acute bolus drug administration (20-40 mg/kg) of METH have been employed frequently to study neurotoxicity in the brain. In this study we have compared these drug delivery schedules to determine their efficacy to induce striatal apoptosis. Exposure of male mice to a binge of METH at 10mg/kg 4x at 2 h intervals (cumulative dose of 40 mg/kg) was approximately four times less effective in inducing apoptotic cell death (TUNEL staining) 24 h after METH treatment in the striatum than a single bolus administration of 30 mg/kg of METH. The residual TUNEL staining observed three days after METH treatment is proportionately equivalent between a binge and the acute bolus drug administration. Interestingly, a binge of METH induces a hyperthermic response of longer duration. This study demonstrates that an acute bolus drug administration of METH is more effective inducing striatal apoptosis in mice, and therefore, is more suitable for studies assessing the impact of METH on sites post-synaptic to the striatonigral dopamine terminals.