Progressive behavioural changes in the spatial open-field in the quinolinic acid rat model of Huntington's disease

Huntington's disease (HD) is a progressive neurodegenerative disorder, characterized by severe degeneration of basal ganglia, motor abnormalities, impaired cognitive functions and emotional disturbances. Intrastriatal injection of the excitotoxin quinolinic acid (QA), an N-methyl-D-aspartate receptor agonist, appears to reproduce in rats some of the clinical features of human HD, included motor and behavioural deficits. Aim of this study was to assess whether the behavioural alterations described in the QA rat model of HD progressed over time. We analysed the effects of bilateral striatal injection of QA (300 nmol/1 microl) to adult rats in the spatial open-field test, a nonaversive task in which exploratory activity and responses to both spatial rearrangement of familiar objects and object novelty are measured. Rats were tested 2 weeks, 2 and 6 months after the QA lesion. Lesioned rats showed progressive alterations in performance in this task. Whereas sham and QA rats did not markedly differ 2 weeks post-lesion, lesioned rats were significantly more active than controls 2 and 6 months after surgery. Specifically, frequency and duration of rearing and wall rearing increased progressively over time, while grooming was enhanced at 2 months post-lesion only. Spatial and object novelty discrimination was not affected. These results show that a single injection of QA excitotoxin can induce behavioural changes that progress over time. The main implication of these findings is that, besides genetic mice models of HD, QA-lesioned rats may represent a suitable mean to test the ability of new drugs to slow down disease progression.