Effects of orbitofrontal, infralimbic and prelimbic cortical lesions on serial spatial reversal learning in the rat

Background: Recent evidence suggests that the neural correlates of reversal learning are localised to the orbitofrontal cortex whereas studies on the contribution of the medial prefrontal cortex to this capacity have produced equivocal results. This study examines the behavioural effects of selective lesions centred on orbitofrontal, infralimbic and prelimbic cortex on serial spatial reversal learning in the rat. Methods: Rats were trained on a novel instrumental two-lever spatial discrimination and reversal learning task, measuring both 'cognitive flexibility' and constituent processes including response inhibition. Both levers were presented, only one of which was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a series of reversals was presented. Results: Bilateral excitotoxic lesions of the orbitofrontal cortex did not affect retention of a preoperatively acquired spatial discrimination but did impair reversal learning. This deficit manifested as increased perseverative responding on the previously correct lever. Although impairments were evident during reversal 1, OFC-lesioned animals performed significantly better than controls on reversal 2. There were no significant effects of infralimbic and prelimbic lesions on the retention of a spatial discrimination or reversal learning. Conclusions: These results indicate that the orbitofrontal cortex is critical for flexible responding in serial spatial reversal learning. The present findings may be relevant to deficits in reversal learning and response inhibition in such neuropsychiatric disorders as obsessive-compulsive disorder. (c) 2007 Elsevier B.V. All rights reserved.