Physical exercise attenuates MPTP-induced deficits in mice

Two experiments were performed to investigate the effects of physical exercise upon the hypokinesia induced by two different types of MPTP administration to C57/BL6 mice. In the first, mice were administered either the standard MPTP dose (2 × 20 or 2 × 40 mg/kg, 24-h interval) or vehicle (saline, 5 ml/kg); and over the following 3 weeks were given daily 30-min period of wheel running exercise over five consecutive days/week or placed in a cage in close proximity to the running wheels. Spontaneous motor activity testing in motor activity test chambers indicated that exercise attenuated the hypokinesic effects of both doses of MPTP upon spontaneous activity or subthreshold L: -Dopa-induced activity. In the second experiment, mice were either given wheel running activity on four consecutive days (30-min period) or placed in a cage nearby and on the fifth day, following motor activity testing over 60 min, injected with either MPTP (1 × 40 mg/kg) or vehicle. An identical procedure was maintained over the following 4 weeks with the exception that neither MPTP nor vehicle was injected after the fifth week. The animals were left alone (without either exercise or MPTP) and tested after 2- and 4-week intervals. Weekly exercise blocked, almost completely, the progressive development of severe hypokinesia in the MPTP mice and partially restored normal levels of activity after administration of subthreshold L: -Dopa, despite the total absence of exercise following the fifth week. In both experiments, MPTP-induced loss of dopamine was attenuated by the respective regime of physical exercise with dopamine integrity more effectively preserved in the first experiment. The present findings are discussed in the context of physical exercise influences upon general plasticity and neuroreparative propensities as well as those specific for the nigrostriatal pathway.