University of North Carolina at Chapel Hill Graduate School
Doi
Abstract
Psychedelics have experienced renewed interest following studies suggesting rapid-acting and long-lasting therapeutic effects in patients with affective psychiatric disorders. While clinical results look promising, the circuit-level neurobiological mechanisms underlying acute and prolonged effects remain unclear. Many psychiatric disorders involve dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The central amygdala (CeA), paraventricular nucleus of the hypothalamus (PVN), and paraventricular nucleus of the thalamus (PVT) are all key regions in orchestrating the neural and endocrine stress response. Here, we aimed to test how a single administration of psilocin, the psychoactive metabolite of psilocybin, alters reactivity of these regions at both acute and prolonged time points in Sprague Dawley rats. We found that a single dose of psilocin (2mg/kg) produces acute increases in reactivity within the PVT and CeA in females, and acute increases in PVN reactivity and prolonged decreases in CeA reactivity in males. The effects in both CeA and PVN seen in males were driven by those employing an active threat responding behavior strategy. We also observed an effect of psilocin administration on maintenance of reactivity within PVTCeA circuitry in both males and females. All together, these data provide intriguing new insight into the region-specific alterations following a single dose of a psychedelic and may serve as a foundation in uncovering the circuit-level mechanisms underlying the acute and persistent effects of psychedelic drug action.Doctor of Philosoph
