MYCOLab Ai Logo - gold and army green

Sex-specific effects of psychedelic drug exposure on central amygdala reactivity and behavioral responding

Summary

Researchers studied how psilocybin’s active form affects the brain’s fear center in both male and female rats. They found that a single dose produced different effects in males versus females, with males showing lasting reductions in fear responses over 28 days while females showed variable changes. These findings help explain why psychedelics might work differently between sexes and could inform how they’re used to treat anxiety and depression in humans.

Background

Psilocybin and psilocin have shown rapid and long-lasting improvements in affective psychiatric illnesses. The central amygdala (CeA) is a primary output region dysregulated in affective psychiatric disorders. Understanding region-specific alterations underlying psychedelic therapeutic effects remains relatively unknown.

Objective

This study investigated sex-specific effects of psilocin on central amygdala activity and reactivity to aversive stimuli. The researchers measured CeA activity using c-Fos expression and CeA reactivity using fiber photometry paired with an aversive air-puff stimulus across acute and prolonged timepoints.

Results

Psilocin acutely increased CeA activity in both sexes and stimulus-specific reactivity in females but not males. Males showed time-dependent decreases in reactivity lasting from 2-28 days post-administration, while females did not. Sex-dependent changes in threat responding were observed, with psilocin promoting passive responses in males. Differential CeA reactivity patterns emerged for auditory stimulus components.

Conclusion

A single dose of psilocin produces sex-specific, time-dependent, and enduring changes in central amygdala reactivity and behavioral responding. These findings suggest males show persistent reductions in fear reactivity while females show variable responses. Results provide preclinical evidence for sex-dependent neurobiological mechanisms underlying psychedelic therapeutic effects.
  • Published in:Translational Psychiatry,
  • Study Type:Preclinical Animal Study,
  • Source: PMID: 37031219
Scroll to Top