The grid-walking test: assessment of sensorimotor deficits after moderate or severe dopamine depletion by 6-hydroxydopamine lesions in the dorsal striatum and medial forebrain bundle

Abstract

The present study aims to evaluate the applicability of the grid-walking test in rats with moderate or severe dopamine-depletion incurred by unilateral nigro-striatal 6-hydroxydopamine (6-OHDA) lesions. Striatum samples were analyzed by high pressure liquid chromatography coupled to electrochemical detection (HPLC-EC) after behavioral testing. In Experiment 1, 2 weeks after the injection of 6-OHDA into the medial forebrain bundle, adult Wistar rats were divided into an l-3,4-dihydroxyphenylalanine (L-dopa) and a vehicle treatment group and their behaviors on the grid were compared. The severely lesioned animals (mean dopamine depletion of 92%) did not exhibit behavioral asymmetry in the number of contralateral foot-slips. However, L-dopa administration selectively reduced the number of foot-slips of the contralateral forelimb when compared with the vehicle group. In Experiment 2, 6-OHDA was injected into the dorsal striatum and foot-slips on the grid were analyzed 4, 9 and 13 days following the lesion. The rats with moderate dopamine-depletion (mean depletion of 54%) exhibited more contralateral forelimb-slips on all testing days. Compared with naive rats, hemiparkinsonian rats also showed more forelimb-slips. These results suggest that the grid-walking test should be a powerful and sensitive behavioral assay for sensory-motor deficits in rat models of nigro-striatal dopamine lesions.