The therapeutic potential of psilocybin for the treatment of neuropsychiatric disorders such as anorexia nervosa (AN) is currently being assessed in clinical trials, and is proposed to act by alleviating the cognitive inflexibility that characterises AN. Our lab has shown preclinically, an impairment in cognitive flexibility in AN, using our activity-based anorexia (ABA) rat model. Additionally, our preliminary data suggests that psilocybin treatment improves weight maintenance in ABA, and that psilocybin treatment in wild-type rats improves cognitive flexibility. Therefore, our overarching aim is to determine whether these outcomes altered by psilocybin treatment are mediated by actions at different serotonin (5-HT) receptors in the rat brain. For this, we use a two-pronged approach, firstly we will disentangle on a fundamental level, how psilocybin improves cognitive flexibility in wild-type rats using home cage and experimenter-free operant testing devices. Secondly, we will determine how psilocybin treatment alters the expression of serotonin receptor subtypes, 5-HT1A and 5-HT2A, using the RNA Scope assay. We specifically focused on the rat prefrontal cortex (PFC), a brain region implicated in the primary aspects of cognitive flexibility and where differences in serotonin receptor expression have been observed in AN. This study will reveal how psilocybin alters 5-HT receptor expression within distinct PFC regions and highlight the necessity of specific 5-HT receptor function for the therapeutic effects of psilocybin on weight maintenance and cognitive flexibility.