Increased reactivity of the paraventricular nucleus of the hypothalamus and decreased threat responding in male rats following psilocin administration.

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.

Study at a glance

Abstract

Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats. Psilocin increased stimulus-independent PVN activity as measured by c-Fos expression in male and female rats. Psilocin increased PVN reactivity to an aversive air-puff stimulus in males but not females. Reactivity was restored at 2- and 7-days post-injection with no group differences. Additionally, prior psilocin injection did not affect PVN reactivity following acute restraint stress. Experimental groups sub-classified by baseline threat responding indicate that increased male PVN reactivity is driven by active threat responders. These findings identify the PVN as a significant site of psychedelic drug action with implications for threat responding behavior.