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.
A single dose of psilocin, the active metabolite of psilocybin, produces sex-specific, time-dependent, and lasting changes in central amygdala (CeA) activity and reactivity to an aversive air-puff stimulus in mice. Psilocin acutely increased CeA activity in both sexes and increased stimulus-specific CeA reactivity in females but not males. In males, psilocin caused time-dependent decreases in reactivity from 2 to 28 days after administration, while females showed no such decrease. Behavioral threat responses also changed in a sex-dependent manner, with no effects on exploratory behavior or locomotion. These findings suggest enduring, sex-specific alterations in CeA function underlie psilocin's therapeutic effects in affective disorders.