A highly sensitive automated complex running wheel test to detect latent motor deficits in the mouse MPTP model of Parkinson's disease

Abstract

The subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) paradigm is one of the most widely used in vivo models of Parkinson's disease (PD). However, particularly in the mouse model it has remained difficult to reliably detect behavioural correlates for PD. In the present study we apply a novel murine motor test, the motor skill sequence (MOSS) based on computerized recording of voluntary running wheel activity, and found latent motor skill deficits in the subchronic MPTP mouse model. Mice are first subjected to a 2-week training phase. The animals then receive either MPTP injections according to the standard subchronic MPTP paradigm (30 mg/kg) or vehicle injections for 5 consecutive days. Running performance transiently fell during the injection phase but returned to baseline within few days. The animals were then exposed to complex wheels with irregularly spaced crossbars demanding high central motor coordination abilities. Though both groups showed clear improvement of running performance in the learning phase on the complex wheel, MPTP animals displayed clear central motor deficits on the complex wheels, as indicated by a reduced maximum speed and running distance, despite unchanged running motivation. Our results demonstrate latent motor deficits in MPTP-treated mice, which can be unmasked by MOSS. MOSS is thus capable of detecting and quantifying central motor deficits in this widely used model of PD with high sensitivity. The automated full time data collection of several different running parameters makes it also a suitable test for efficient in vivo screening of potential therapeutic compounds in this model for PD.