Advisor(s)
Phillip R Zoladz, Professor of Psychology
Confirmation
1
Document Type
Poster
Location
McIntosh Activities Room
Start Date
19-4-2024 12:00 PM
End Date
19-4-2024 12:50 PM
Abstract
Fear-related psychological disorders, such as specific phobias and post-traumatic stress disorder (PTSD), represent a major public health issue. It is thought that these disorders develop, at least in part, through fear conditioning processes. Thus, treatment often involves exposure therapy, a technique based on the concept of extinction. However, this type of therapy is ineffective for many individuals. To augment extinction learning, researchers have paired exposure therapy with pharmacological agents that enhance neuroplasticity (e.g., D-cycloserine), but the results of such manipulations have been inconsistent. It is possible that psychedelics, which have been largely unexplored in their ability to enhance extinction learning, could aid in exposure therapy. Indeed, preclinical research suggests that several psychedelic substances, such as MDMA and DMT, enhance synaptic plasticity. Thus, we explored the dose-dependent effects of the 5-HT2A agonist psilocybin on fear extinction in adult rats.
On Day 1, adult male and female Sprague-Dawley rats were placed in a fear conditioning chamber (Context A). Following a 3-min acclimation phase, the rats were presented with 5 tones (10-sec, 2-kHz) that each co-terminated 1-sec, 1-mA footshocks; there was a 60-sec interstimulus interval (ISI) following each tone-shock pairing. On Day 2, the rats were injected intraperitoneally with psilocybin (0.3 or 1 mg/kg) or vehicle (0.9% saline) 30 min prior to undergoing fear extinction in a novel environment (Context B). During extinction, the rats were given a 3-min acclimation phase, followed by 30 tone presentations (60-sec ISIs) without any footshock. On Day 4, rats underwent extinction recall by being placed in Context B; the test began with a 3-min acclimation phase, followed by 10 tone presentations (60-sec ISIs) without any footshock. Freezing behavior was quantified by FreezeFrame software (Actimetrics, Inc.). Analyses of freezing behavior during training and early extinction demonstrated that all rats developed strong fear of the tone. Most importantly, the low dose of psilocybin enhanced extinction learning in males but slowed extinction learning in females. This differential impact of psilocybin on extinction was maintained during extinction recall the next day. Our findings suggest that a low dose of psilocybin augments extinction learning in males, but not females. The sex-dependent nature of this effect warrants additional research.
Recommended Citation
Miller, Claire E.; Naylor, Margaret M.; Del Valle, Colin R.; Sparkman, Heather R.; Bramlage, Brooke E.; Puppel, Lillianna P.; Al-Olimat, Aleece K.; King, Kylie M.; Savini, Marisa J.; and Zoladz, Phillip R., "Low-dose psilocybin sex-dependently enhances fear extinction in adult rats" (2024). ONU Student Research Colloquium. 49.
https://digitalcommons.onu.edu/student_research_colloquium/2024/Posters/49
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Low-dose psilocybin sex-dependently enhances fear extinction in adult rats
McIntosh Activities Room
Fear-related psychological disorders, such as specific phobias and post-traumatic stress disorder (PTSD), represent a major public health issue. It is thought that these disorders develop, at least in part, through fear conditioning processes. Thus, treatment often involves exposure therapy, a technique based on the concept of extinction. However, this type of therapy is ineffective for many individuals. To augment extinction learning, researchers have paired exposure therapy with pharmacological agents that enhance neuroplasticity (e.g., D-cycloserine), but the results of such manipulations have been inconsistent. It is possible that psychedelics, which have been largely unexplored in their ability to enhance extinction learning, could aid in exposure therapy. Indeed, preclinical research suggests that several psychedelic substances, such as MDMA and DMT, enhance synaptic plasticity. Thus, we explored the dose-dependent effects of the 5-HT2A agonist psilocybin on fear extinction in adult rats.
On Day 1, adult male and female Sprague-Dawley rats were placed in a fear conditioning chamber (Context A). Following a 3-min acclimation phase, the rats were presented with 5 tones (10-sec, 2-kHz) that each co-terminated 1-sec, 1-mA footshocks; there was a 60-sec interstimulus interval (ISI) following each tone-shock pairing. On Day 2, the rats were injected intraperitoneally with psilocybin (0.3 or 1 mg/kg) or vehicle (0.9% saline) 30 min prior to undergoing fear extinction in a novel environment (Context B). During extinction, the rats were given a 3-min acclimation phase, followed by 30 tone presentations (60-sec ISIs) without any footshock. On Day 4, rats underwent extinction recall by being placed in Context B; the test began with a 3-min acclimation phase, followed by 10 tone presentations (60-sec ISIs) without any footshock. Freezing behavior was quantified by FreezeFrame software (Actimetrics, Inc.). Analyses of freezing behavior during training and early extinction demonstrated that all rats developed strong fear of the tone. Most importantly, the low dose of psilocybin enhanced extinction learning in males but slowed extinction learning in females. This differential impact of psilocybin on extinction was maintained during extinction recall the next day. Our findings suggest that a low dose of psilocybin augments extinction learning in males, but not females. The sex-dependent nature of this effect warrants additional research.