The effect of URB597, exercise or their combination on the performance of 6-OHDA mouse model of Parkinson disease in the elevated plus maze, tail suspension test and step-down task.

Parkinson disease (PD) is a progressive neurodegenerative disorder that is often accompanied by motor and psychiatric symptoms. Various approaches have been proposed for the treatment of PD. Here, we investigated the effect of a low dose of fatty acid amide hydrolase inhibitor URB597 (as an enhancer of endocannabinoid anandamide levels), exercise or their combination on some behavior alterations in PD mice lesioned by 6-hydroxydopamine (6-OHDA). The impact of swimming exercise (5×/week for 4 weeks) and URB597 (0.1 mg/kg, 2×/week for 4 weeks) on the anxiety-related behavior (elevated plus maze; EPM), depression-related behavior (tail suspension test; TST), and passive avoidance memory (step-down task) was examined in the sham and male NMRI mouse of PD model. The results show that URB597 prevented memory deficits and elicited antidepressant- and anxiolytic-like effects but did not affect hypolocomotion in the PD mice. However, URB597 did not have a significant effect on the performance of the sham mice in the performed tests. Moreover, swimming training abolished depressive- and anxiogenic-like behaviors and increased locomotion without affecting memory deficits in the PD mice. Meanwhile, swimming decreased immobility time and increased locomotion in the sham mice. Furthermore, URB597 in association with swimming training prevented all deficits induced in the PD mice, while this combination impaired memory and produced the positive effects on depression- and anxiety-related behaviors and locomotion of the sham mice. It is concluded that although URB597 or exercise alone had positive effects on most behavioral tests, their combination improved all parameters in the PD mice.