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 specific mechanisms behind these therapeutic effects remain relatively unknown. The central amygdala (CeA) is a primary output region within the extended amygdala that is heavily dysregulated in affective psychiatric disorders. Here, we utilized fiber photometry to measure changes in CeA reactivity to an aversive air puff stimulus after psilocin administration, both acutely and at varying prolonged time points. We found that administration of psilocin increased reactivity acutely in females, but not males. Additionally, we show that one dose of psilocin produced decreases in reactivity in males, but not females, 28-days post administration, with decreases seen as early as 2-days post administration. We further report stimulus-specific changes in CeA reactivity after psilocin with differential responsivity to an aversive air puff stimulus and an auditory stimulus. We also measured changes in behavioral response to the air puff stimulus and report sex differences in exploratory behavior but not threat responding or general locomotion. This study provides evidence that a single dose of psilocin can elicit sex-specific, dynamic, and enduring changes in CeA reactivity to an aversive stimulus. These data are an important step towards dissecting circuit-based mechanisms underlying the effects of psychedelics.

Datasets include two matlab structures that were constructed using the .m scripts included. Subjects that were removed from study were then removed from data before saving as structure.

In order to use these scripts you need to have the TDTSDK folder from TDT which allows for processing of raw data files. Additionally you would need the raw data files from the study. However, using the matlab (.mat) structures provided, you are able to process data using the GroupDataAnalysis_BinnedData120521.m script.