The role of the orbitofrontal cortex in the cognitive flexibility of rats assessed using novel touchscreen-based tasks

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The orbitofrontal cortex (OFC) is critical for cognitive flexibility that aids organisms to adapt their behavioural within the ever-changing environments. Its role in flexible behaviour is typically assessed using tasks in which subjects must change an established behavioural response in order to adapt to new contingencies. In the present study, two tasks were performed to investigate the role of the OFC in rats. This was assessed by using novel touchscreen-based tasks. One of these tasks is the serial reversal learning, a test that was per-formed to explore the role of the OFC when the contingencies of the visual stimuli are reversed, specifically, when the rats receive different doses of the 5-HT2c receptor antagonist SB242084. This task used two visual cues, one positive (CS+) and one negative (CS-). Touching the screen was required for reward delivery. After training, rats received intra-OFC infusions via cannulae during the reversals. In the rats, reversal learning was significantly enhanced when receiving the 1.0 µg/ml dose, but not when receiving the vehicle or 3.0 µg/ml. This effect was shown only during the perseverative phase and thus seems phase-specific. The second ex-periment that was performed is the intra-dimensional/ extra-dimensional (IDED) set shifting task. This is a test composed of different stages to measure rule acquisition and reversal. Again the task started with two visual cues during training. After that, the rats received exocitotic lesions in the medial orbitofrontal cortex (mOFC), the lateral orbitofrontal cortex (lOFC) or sham lesions. The rats were able to perform intra-dimensional set-shifting stages and therefore were able to form a dimensional set. These set shifting results also yielded differences between the lateral and medial OFC lesioned animals. Lesions in the mOFC showed enhanced intra-dimensional set shifting compared to the lateral and sham lesion groups. The reversal re-sults, on the other hand, showed no clear differences between any of the groups. These results provide the first direct evidence from touchscreen-based tasks for the involvement of the 5-HT2c receptor in enhancing the perseverative phase of reversal learning. Moreover, they provide evidence for dissociable functional roles of the mOFC and lOFC during the performance of intra-dimensional set shifting.
Faculteit der Sociale Wetenschappen