Research reportA comparison of voluntary and forced exercise in protecting against behavioral asymmetry in a juvenile hemiparkinsonian rat model

•Starting exercise after weaning before an adult 6-OHDA lesion is a novel design.•Preconditioning of exercise did not prevent motor asymmetry in a 6-OHDA rat model.•No differences between forced and voluntary exercise were observed.•These results are inconsistent with research showing exercise to be neuroprotective.

Several studies have found a neuroprotective effect of forced exercise in rodent Parkinson's disease models; however, the evidence for the protective effect of voluntary exercise is mixed. Most of these studies have initiated the exercise after toxin-induced hemiparkinsonism. Few studies have investigated the role of a preconditioning of exercise prior to neurotoxic insult. Therefore, the purpose of this study was to explore the neuroprotective effect of regular forced and voluntary exercise in recently weaned rat pups prior to an adult hemiparkinsonian lesion. Recently weaned rat pups were randomized into four 6-week experimental groups: forced exercise, voluntary exercise, control, and a sham surgery control. After participation in a 6-week experimental condition, hemiparkinsonism was induced using a unilateral injection of 6-hydroxydopamine (6-OHDA). Parkinsonian behavioral tests (i.e., apomorphine rotations, forelimb placement asymmetry, exploratory rearing) demonstrated significant motor asymmetry for all three 6-OHDA group; however, there were no significant differences among them. The sham control rats did not show motor impairment consistent with nigrostriatal motor deficits. Neither a preconditioning of forced nor voluntary exercise was neuroprotective of a future 6-OHDA lesion. These results are in contrast to the literature and suggest that exercise neuroprotection may not be so straightforward.