Research ReportForced exercise before or after induction of 6-OHDA-mediated nigrostriatal insult does not mitigate behavioral asymmetry in a hemiparkinsonian rat model

- A preconditioning of forced exercise prior to the onset of 6-OHDA-induced hemiparkinsonism did not protect against behavioral asymmetry.
- Forced exercise after the onset of 6-OHDA-induced hemiparkinsonism did not recover behavioral asymmetry.
- These results are inconsistent with research showing exercise to be neuroprotective.

Studies on exercise before and after toxin-induced hemiparkinsonism have reported promising findings in terms of amelioration of motor asymmetry in adult, 6-hydroxydopamine (6-OHDA) rats. However, recent studies have had more mixed results. Therefore, the purpose of this study was to further explore the notion of exercise, in particular forced exercise, as a potential neuroprotective therapy when implemented before and after 6-OHDA hemiparkinsonism. To explore this, two experiments were conducted: Experiment 1 - exercise before a 6-OHDA lesion; and, Experiment 2 - exercise after a 6-OHDA lesion. In Experiment 1, rats were randomly assigned into one of the two 4-week experimental conditions, a forced exercise condition and a non-exercise control condition. Then, after the experimental conditions rats were injected with 6-OHDA into the right medial forebrain bundle. In Experiment 2, rats were first injected with 6-OHDA and were then randomly assigned into one of the two 4-week experimental groups, a forced exercise group and a non-exercise control group. Outcomes in both experiments did not show any differences in terms of motor behavioral tests (i.e., apomorphine rotations, forelimb placement asymmetry, exploratory rearing) between the forced exercise and sedentary control groups. Based on our results and in light of the body of literature, it is possible that the stress of shock-motivated forced running utilized in this study may have canceled beneficial behavioral effects. Additionally, it is possible that the one-week delay in the forced exercise protocol implementation in Experiment 2 may have prevented behavioral rescue.