Botulinum neurotoxin-a injected intrastriatally into hemiparkinsonian rats improves the initiation time for left and right forelimbs in both forehand and backhand directions

Abstract

Forelimb stepping is a widely used test for the assessment of forelimb akinesia in hemiparkinsonian (hemi-PD) rats. The initiation time (IT) is considered the most sensitive parameter in the stepping test procedure. Here we propose a novel, reliable, and simple method for the measurement of IT of both forelimbs in both forehand and backhand directions in rats. Evaluating the same videos taken for quantifying adjusting steps, IT measurements were done without additional experiments. This is in contrast to the classical approach introduced by Olsson et al. (1995), in which separate experiments are necessary. We successfully applied our approach to hemi-PD rats intrastriatally treated with botulinum neurotoxin-A (BoNT-A). In naive rats, an IT of about 0.62 s was found, and in right-sided hemi-PD rats the IT of the left forepaw increased to about 3.62 s. These hemi-PD rats showed, however, reduced ITs of the impaired left forepaws 1 month and the second time 7 months after induction of hemi-PD via the injection of 1 ng BoNT-A into the ipsilateral striatum, depending on post BoNT-A survival time. The method described offers the possibility of a precise and animal-friendly evaluation of IT in rats, including the beneficial effect of BoNT-A treatment in hemi-PD rats.