Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms
Molecular Psychiatry April 27, 2024 K Conn, L K Milton, K Huang et al. 44 citations
Psilocybin, currently in clinical trials for anorexia nervosa (AN), may improve cognitive inflexibility, a core feature of AN. Using the activity-based anorexia rat model, psilocybin post-acutely improved body weight maintenance in female rats and facilitated cognitive flexibility, specifically through better adaptation to reversed reward contingencies. The cognitive enhancing effects involved serotonin 5-HT1A and 5-HT2A receptor signaling; blocking 5-HT1A negated these benefits. Psilocybin transiently increased cortical Htr2a transcription and decreased Htr1a transcription, with further Htr2a reduction in anorexic rats. These findings suggest psilocybin could ameliorate cognitive inflexibility in AN and highlight therapeutic mechanisms beyond 5-HT2A receptor binding.