Examination Date
Spring 1-29-2026
Degree
Dissertation
Degree Program
Pharmacology and Experimental Therapeutics
Examination Committee
Dr. Charles D. Nichols, Dr. Scott Edwards, Dr. Dennis Paul, Dr. Peter Winsauer, Dr. Andrew Catling
Abstract
Psilocybin is emerging as a potential long-lasting treatment for major depressive disorder, but the downstream mechanisms underlying its antidepressant effects remain unclear. Psilocin, the activate metabolite of psilocybin, mediates its psychoactive effects primarily through activation of 5-HT2A receptors. Preclinical studies demonstrate a single 1 mg/kg dose produces sustained antidepressant-like effects in the forced swim test, persisting for more than five weeks. To investigate the molecular basis of these effects, the present study characterized expression of immediate early genes and AMPA and NMDA receptor subunits in male and female Wistar Kyoto rats at 2 hours, 24 hours, and 5 weeks following a single 1 mg/kg dose of psilocybin or saline. Analyses were conducted across medial prefrontal cortex subregions, including the anterior cingulate, prelimbic, and infralimbic cortices.
Psilocybin induced robust increases in immediate early gene expression at 2 hours but produced almost no differences at other time points. In contrast, sex- and time-dependent effects were observed for AMPA and NMDA receptor subunits across all time points. Widespread sexually dimorphic expression was present across subregions at 2- and 24-hour time points but was largely restricted to the infralimbic cortex at 5 weeks. This shift may reflect age-related differences, as animals in the 5-week cohort were older at the time of sacrifice. Time-dependent effects appeared between the 2-hour and 24-hour cohorts, likely reflecting a 2-hour difference in sacrifice time, with significant differences observed in 14 out of 15 genes across subregions.
Together, these findings indicate that gene expression in the medial prefrontal cortex is strongly influenced by sex and time of sacrifice, while psilocybin administration produces little to no detectable changes in glutamatergic receptor expression in bulk tissue. These results suggest that the sustained antidepressant-like effects may not be mediated by long-term changes in receptor abundance among all cell types but instead may reflect functional adaptations or cell type-specific changes.
Recommended Citation
Kramer, Hannah M., "The Effects of Psilocybin, Sex, and Time on Gene Expression in the Medial Prefrontal Cortex of Wistar Kyoto Rats" (2026). School of Graduate Studies. 21.
https://digitalscholar.lsuhsc.edu/etd_sgs/21
Dissertation Report Form