Repetitive vibrissae-elicited forelimb placing before and immediately after unilateral 6-hydroxydopamine improves outcome in a model of Parkinson's disease

Abstract

In rodent models of Parkinson's disease (PD), exercise or complex living environments introduced immediately before or during early stages of degeneration can provide beneficial effects on functional and/or neurochemical outcome. The goal of this study was to determine whether or not exposure to repetitive vibrissae-elicited forelimb placing, a dopamine-dependent sensorimotor movement, improves functional outcome in rats infused unilaterally with 6-OHDA. Prior to unilateral 6-OHDA infusions into the medial forebrain bundle, male Sprague-Dawley rats were randomly divided into groups exposed to one of five placing schedules: (1) two consecutive days pre-6-OHDA (PRE), (2) PRE+day 1 post-6-OHDA, (3) PRE+days 1, 2, 3 post-6-OHDA, (4) HANDLE, and (5) Sham infusion+handle. A session consisted of 180 total trials (90 left forelimb and 90 right forelimb trials) including 60 consecutive trials where vibrissae stimulation evoked ipsilateral forelimb movement and 30 consecutive trials where the ipsilateral forelimb was restrained so that vibrissae evoked contralateral forelimb movement (cross-midline placing). All groups were exposed to forelimb placing sessions on post-infusion days 7 and 14. The ability of vibrissae stimulation to elicit an ipsilateral response of the 6-OHDA affected forelimb was assessed on all days. Animals were sacrificed on post-lesion day 15 and substantia nigra tyrosine hydroxylase immunoreactivity (TH-ir) quantified. Repetitive forelimb placing had a significant effect on behavioral performance for all groups compared to the HANDLE group, but only the PRE+123 group was not significantly different from SHAM controls. Only the PRE+123 group showed significant sparing of TH-ir compared to the HANDLE group. These data suggest that extensive repetitive exposure to a sensorimotor task may provide therapeutic effects in an animal model of PD.