Role of Endogenous Cannabinoid Signaling in the Medial Prefrontal Cortex in Cognitive Flexibility
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The prefrontal cortex (PFC) is the center for executive functioning, overseeing cognitive strategies according to changing environmental demands. The endogenous cannabinoid (ECB) system is expressed throughout the PFC contributing to numerous PFC-mediated behaviors. However, the extent to which ECB signaling in the PFC influences cognitive flexibility has yet to be evaluated. Our study investigates whether pharmacological blockade of ECB signaling within the medial PFC (mPFC) alters cue discrimination learning and cognitive flexibility in a strategy-shifting task. Male adult rats were trained to press a lever in response to illuminated visual cues to obtain a food reward. To determine the involvement of mPFC ECB signaling in acquiring visual cue discrimination, rats received microinfusions of the CB1 receptor antagonist rimonabant (0.3µg/0.2µL/side), or an equivalent volume of vehicle before testing. Subsequently, rats were tested in the strategy-shifting task, which required them to disregard the previously learned strategy in favor of an egocentric spatial learning strategy (i.e., always press left lever regardless of the cue). Rats again received counterbalanced microinfusions prior to testing, and the number of trials to criterion and errors were tabulated. Contrary to our hypothesis, preliminary results indicate that intra-mPFC CB1 receptor inactivation does not significantly alter visual cue discrimination learning or strategy shifting performance. Although, the number of rats per group should be increased before firm conclusions can be drawn, these pilot data indicate that ECB signaling at CB1 receptors in the mPFC is not necessary for learning or switching behavioral strategies in this cognitive flexibility task.