BILATERAL LESIONS OF THE SUBTHALAMIC NUCLEUS INDUCE MULTIPLE DEFICITSIN AN ATTENTIONAL TASK IN RATS

Lesioning the subthalamic nucleus (STN) has been suggested as possible therapy for the treatment of parkinsonism. Previous experiments inves tigating this hypothesis in rats confirmed that excitotoxic STN lesion s alleviate the motor impairment induced by striatal dopamine depletio n, which reproduced the degeneration observed in parkinsonism, but eli cited presumed non-motor deficits such as premature responding, sugges ting that the STN could be involved in other aspects of response contr ol. The aim of the present study was to extend this analysis to choice paradigms. We thus investigated the behavioural effects of bilateral excitotoxic lesions of the STN in rats performing a five-choice test o f divided and sustained visual attention, modelled on the human contin uous performance task. This task required the animals to detect a brie f visual stimulus presented in one of five possible locations and resp ond by a nose-poke in this illuminated hole within a fixed delay, for food reinforcement. Bilateral lesions of the STN severely impaired sev eral aspects of performance, including discriminative accuracy, but al so increased premature, anticipatory responding as well as perseverati ve panel pushes and nose-poke responses. While increasing the stimulus duration and reducing the wailing period for the stimulus partially a lleviated the accuracy deficit and the premature responding deficit re spectively, other deficits, such as perseverative panel pushes and nos e-poke responses, were sustained under these conditions. Systemic inje ction of the mixed dopaminergic D1/D2 receptor antagonist, alpha-flupe nthixol (0.03-0.18 mg/kg), reduced premature responses and perseverati ve panel pushing without affecting the perseverative nose-poke respons es, suggesting that some of the deficits were independent of striatal dopaminergic transmission. These results suggest that STN lesions have multiple, dissociable effects on attentional performance, including d iscriminative deficits, impulsivity and perseverative behaviour. They ape consistent in part with a hypothesized role of the STN in recent m odels of basal ganglia function in action selection and inhibition. Th e results also show that other aspects of behaviour should be monitore d when examining the capacity of STN lesions to reverse the parkinsoni an deficit induced by striatal dopamine depletion.