Does Repeated Methamphetamine Exposure at Different Regimens Cause Parkinsonian-Like Behavior in Rats?

Abstract

Methamphetamine (MA), a highly addictive psychostimulant, produces long-lasting neurotoxic effects well proven in nigrostriatal dopaminergic neurons. Considering the similarities between pathological profile of MA neurotoxicity and Parkinson's disease (PD), some reports show that previous MA abusers will be at greater risk of PD-like motor deficits. To answer the question if repeated MA exposure causes parkinsonian-like behavior in rats, we used three regimens of MA administration and assessed the motor performance parameters immediately and over a long period after MA discontinuation. Male Wistar rats in two experimental groups were treated with escalating paradigms consisting of twice daily intraperitoneal injection of either 1-7 mg/kg or 1-14 mg/kg of MA over 14 days. The third group received twice-daily doses of 15 mg/kg of MA every other day for total number of 7 days. At the 1st, 7th, 14th, 21st, 28th, and 60th days after last injections, motor activities were evaluated using narrow beam, pole, and rotarod tests. Locomotor activity was also evaluated using open field test. Repeated-measures ANOVA indicated that over the two months period following MA exposure, drug-treated rats perform beam, pole, and rotarod tests equally well as their corresponding vehicle-treated controls. Comparison of the locomotor activity didn't show significant differences between groups. These data indicated that MA at these regimens does not cause PD-related motor deficits in rats. Since MA doses, exposure duration, and dosing intervals have been shown to affect MA-induced dopaminergic toxicity, it can be concluded that none of these regimens; are strong enough to produce measurable behavioral motor deficits in rat.