Psilocin, the psychoactive metabolite of psilocybin, increases activity in the paraventricular nucleus of the hypothalamus (PVN) in rats, a brain region central to stress response, autonomic function, and social behavior. In male rats, psilocin heightened PVN reactivity to an aversive air-puff stimulus, driven by active threat responders, while females showed no such increase. This effect was temporary, with reactivity returning to baseline 2 and 7 days after injection. Prior psilocin did not alter PVN reactivity during acute restraint stress. The findings identify the PVN as a key site of psychedelic action with implications for threat-related behavior.
Psilocin, the active metabolite of psilocybin, acutely reduced voluntary ethanol consumption in mice exposed to two models of chronic ethanol exposure without altering locomotor behavior. It increased activation of the central amygdala (CeA) and decreased relative activation of corticotropin-releasing factor type 1 (CRF1) receptors in CeA subregions of ethanol-naive female mice, with similar effects observed in chronic ethanol-exposed mice at 24 and 72 hours of withdrawal. Psilocin also elevated corticosterone levels at 24 hours but not at 72 hours of withdrawal. These findings indicate that psilocin engages CeA circuitry and reduces relative CRF1 activation alongside acute reductions in drinking, helping explain potential therapeutic mechanisms for alcohol use disorder.