Amelioration of behavioral deficits in a rat model of Huntington's disease by an excitotoxic lesion to the globus pallidus

Abstract

Four groups of rats, sustaining a striatal quinolinic acid (QA) lesion, a pallidal QA lesion, a combined striatal + pallidal lesion, or sham operation, were tested in spontaneous and amphetamine-induced activity, spatial navigation in a water maze, position discrimination and reversal in a wet T maze, and food manipulation. The striatal lesion markedly impaired rats' performance on the motor and cognitive tasks. In contrast, rats sustaining a bilateral lesion to the GP in addition to the striatal lesion performed similarly to sham-operated rats on the motor and cognitive tasks, although they showed a transient decrease in activity levels. Given that a similar dysfunction of basal ganglia circuitry is thought to subserve the behavioral alterations seen in QA-lesioned rats and Huntington's disease (HD) patients, the present results raise the possibility that manipulations of the external segment of the globus pallidus (the primate analogue of the rat GP) could ameliorate some of HD symptoms.