Sex-specific effects of psychedelic drug exposure on central amygdala reactivity and behavioral responding.
Translational psychiatry – April 08, 2023
Source: PubMed
Summary
Psychedelic compounds affect men and women differently when processing fear and threats in the brain. Scientists found that psilocin, the active component in magic mushrooms, changes activity in a key emotional brain region called the amygdala in distinct ways between sexes. While females showed increased reactivity to threatening stimuli immediately after treatment, males experienced reduced fear responses that lasted up to 28 days. These findings help explain why psychedelics may work differently across genders in treating anxiety and mood disorders.
Abstract
Psilocybin and its active metabolite psilocin have been shown to elicit rapid and long-lasting symptom improvements in a variety of affective psychiatric illnesses. However, the region-specific alterations underlying these therapeutic effects remain relatively unknown. The central amygdala (CeA) is a primary output region within the extended amygdala that is dysregulated in affective psychiatric disorders. Here, we measured CeA activity using the activity marker c-Fos and CeA reactivity using fiber photometry paired with an aversive air-puff stimulus. We found that psilocin administration acutely increased CeA activity in both males and females and increased stimulus specific CeA reactivity in females, but not males. In contrast, psilocin produced time-dependent decreases in reactivity in males, but not in females, as early as 2 days and lasting to 28 days post administration. We also measured behavioral responses to the air-puff stimulus and found sex-dependent changes in threat responding but not exploratory behavior or general locomotion. Repeated presentations of the auditory component of the air-puff were also performed and sex-specific effects of psilocin on CeA reactivity to the auditory-alone stimulus were also observed. This study provides new evidence that a single dose of psilocin produces sex-specific, time-dependent, and enduring changes in CeA reactivity and behavioral responding to specific components of an aversive stimulus.