Advisor(s)
Phillip Zoladz
Confirmation
1
Document Type
Poster
Location
ONU McIntosh Center; Activities Room
Start Date
11-4-2025 12:00 PM
End Date
11-4-2025 12:50 PM
Abstract
Fear-related disorders are often treated with exposure therapy, a technique based on the concept of extinction. However, this type of therapy is ineffective for many individuals, so finding a pharmacological adjunct that augments the extinction of fear could lead to better treatment outcomes. In recent preclinical work, investigators have shown that psychedelics can accelerate the extinction of fear, potentially through their impact on neurotrophic signaling. We previously found that psilocybin exerted sex-dependent effects on the extinction of conditioned fear to an isolated cue (i.e., a tone). Specifically, psilocybin enhanced the extinction of cue fear in male rats but impaired it in female rats. In the present study, we extended this work by examining the dose-dependent effects of psilocybin on the extinction of contextual fear, as well as the expression of brain-derived neurotrophic factor (BDNF) in several brain regions.
On Day 1, adult male and female Sprague-Dawley rats were placed in a fear conditioning chamber, and following a 3-min acclimation period, were exposed to 5 unsignaled footshocks (2-sec, 1.5 mA), each separated by 60 sec. On Day 2, the rats were injected intraperitoneally with psilocybin (0.1, 0.3, 0.6, or 1 mg/kg) or vehicle (0.9% saline), and thirty minutes later, they underwent fear extinction by being placed in the same context as Day 1 for 10 min. On Day 3, the rats underwent extinction recall by being placed in the same context as Days 1 and 2 for 10 min. Freezing behavior was quantified by the FreezeFrame software (Actimetrics, Inc.). One hour after extinction recall on Day 3, rat brains were collected; the hippocampus, amygdala, and prefrontal cortex (PFC) were dissected and subsequently processed for BDNF expression via Western blotting.
Analyses of freezing behavior during training and early extinction demonstrated that all rats developed strong fear for the context. Although psilocybin had no significant impact on the extinction of contextual fear in males, it significantly impaired the extinction of contextual fear in females. Specifically, female rats treated with psilocybin, particularly doses above 0.3 mg/kg, exhibited greater freezing than controls during extinction recall on Day 3. Psilocybin had no significant impact on BDNF expression in female rats. However, a low dose of psilocybin (0.3 mg/kg), one that we previously reported to enhance the extinction of cue fear in males, led to reduced BDNF expression in the PFC of male rats. The observed behavioral findings are consistent with our previous work in females and, once again, suggest that psilocybin may exert sex-dependent effects on the extinction of conditioned fear.
Recommended Citation
Puppel, Lillianna P.; Al-Olimat, Aleece K.; King, Kylie M.; Savini, Marisa J.; Miller, Claire E.; Del Valle, Colin R.; Sparkman, Heather R.; Bramlage, Brooke E.; and Zoladz, Phillip R., "Psilocybin impairs the extinction of contextual fear in adult female, but not male, rats" (2025). ONU Student Research Colloquium. 73.
https://digitalcommons.onu.edu/student_research_colloquium/2025/Posters/73
Level of Access
Open Access
Open Access
Available to all.
Included in
Behavioral Neurobiology Commons, Behavior and Behavior Mechanisms Commons, Biological Psychology Commons, Pharmacology Commons
Psilocybin impairs the extinction of contextual fear in adult female, but not male, rats
ONU McIntosh Center; Activities Room
Fear-related disorders are often treated with exposure therapy, a technique based on the concept of extinction. However, this type of therapy is ineffective for many individuals, so finding a pharmacological adjunct that augments the extinction of fear could lead to better treatment outcomes. In recent preclinical work, investigators have shown that psychedelics can accelerate the extinction of fear, potentially through their impact on neurotrophic signaling. We previously found that psilocybin exerted sex-dependent effects on the extinction of conditioned fear to an isolated cue (i.e., a tone). Specifically, psilocybin enhanced the extinction of cue fear in male rats but impaired it in female rats. In the present study, we extended this work by examining the dose-dependent effects of psilocybin on the extinction of contextual fear, as well as the expression of brain-derived neurotrophic factor (BDNF) in several brain regions.
On Day 1, adult male and female Sprague-Dawley rats were placed in a fear conditioning chamber, and following a 3-min acclimation period, were exposed to 5 unsignaled footshocks (2-sec, 1.5 mA), each separated by 60 sec. On Day 2, the rats were injected intraperitoneally with psilocybin (0.1, 0.3, 0.6, or 1 mg/kg) or vehicle (0.9% saline), and thirty minutes later, they underwent fear extinction by being placed in the same context as Day 1 for 10 min. On Day 3, the rats underwent extinction recall by being placed in the same context as Days 1 and 2 for 10 min. Freezing behavior was quantified by the FreezeFrame software (Actimetrics, Inc.). One hour after extinction recall on Day 3, rat brains were collected; the hippocampus, amygdala, and prefrontal cortex (PFC) were dissected and subsequently processed for BDNF expression via Western blotting.
Analyses of freezing behavior during training and early extinction demonstrated that all rats developed strong fear for the context. Although psilocybin had no significant impact on the extinction of contextual fear in males, it significantly impaired the extinction of contextual fear in females. Specifically, female rats treated with psilocybin, particularly doses above 0.3 mg/kg, exhibited greater freezing than controls during extinction recall on Day 3. Psilocybin had no significant impact on BDNF expression in female rats. However, a low dose of psilocybin (0.3 mg/kg), one that we previously reported to enhance the extinction of cue fear in males, led to reduced BDNF expression in the PFC of male rats. The observed behavioral findings are consistent with our previous work in females and, once again, suggest that psilocybin may exert sex-dependent effects on the extinction of conditioned fear.