Motor impairments after methamphetamine-induced neurotoxicity in the rat

Methamphetamine is a psychomotor stimulant which, given in high doses, produces neurodegenerative changes in the dopamine and serotonin systems. This study was designed to assess motoric deficits in the rat following a high-dose regimen of methamphetamine. Long-Evans male rats received either four injections of saline or methamphetamine (12.5 mg/kg, every 2 hr), a dose sufficient to produce 45 and 36% reductions in striatal dopamine and serotonin, respectively. Before treatment, subjects were trained to perform one of the following motor tasks: one-way active avoidance, inhibitory avoidance, rotorod or the balance beam. After recovery, performance under base-line and drug challenge conditions revealed that methamphetamine treatment caused significant deficits in active avoidance performance (24% increase in response latency) and balance beam performance (2- to 3-fold increase in footfalls), but had no effect on inhibitory avoidance or rotorod performance. Administration of l-dopa (100 mg/kg) significantly improved the methamphetamine-treated subjects' performance on the balance beam, but had no effect on the control subjects' performance. The methamphetamine-treated subjects exhibited a significant decrease in sensitivity to the effects of fenfluramine in comparison to the controls on both the rotorod and active avoidance tasks. We conclude that high-dose methamphetamine treatment produces long-lasting motor deficits associated with chronic reductions of striatal dopamine and serotonin. These data and the utility of the motor tasks are discussed in reference to a laboratory model of Parkinson's disease.