Psilocybin prevents activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms
bioRxiv (Cold Spring Harbor Laboratory) December 13, 2023 Kyna‐anne Conn, Lk Milton, Kaixin Huang et al. 6 citations preprint
In a rat model of anorexia nervosa (activity-based anorexia), psilocybin improved body weight maintenance and facilitated cognitive flexibility, particularly by enhancing adaptation when reward contingencies were reversed. The cognitive benefits depended on signaling through the serotonin 5-HT1A receptor, as blocking that receptor negated the effects. Psilocybin also transiently altered cortical expression of serotonin receptor genes, increasing Htr2a and decreasing Htr1a transcripts, with a further reduction in Htr2a in anorexic-model rats. These findings suggest psilocybin could help break cognitive inflexibility in anorexia nervosa and indicate that therapeutic mechanisms may extend beyond 5-HT2A receptor binding.