Behavioral Alterations in THC and Alcohol Co-Use: Insights into Fear Learning and Implications of mGlu5 Modulation
Abstract
Cannabis is one of the most used illicit drugs, particularly in vulnerable populations such as veterans diagnosed with PTSD, adolescents, and those diagnosed with Alcohol Use Disorder. With increased legalization of recreational marijuana use across the United States, it is vital to understand the combined effects of THC and other commonly used drugs. Delta-9-tetrahydrocannabinol (THC), the psychoactive compound found in cannabis, has been shown to significantly impact both physiological and behavioral outcomes related to fear memory when used concomitantly with alcohol. Our lab aims to study these deficits and to investigate the benefits of mGlu5 modulation with CDPPB, a compound used to enhance extinction learning in models of drug dependence. The current study aimed to test the hypothesis that combined THC and alcohol exposure exacerbates fear learning, and extinction of fear can be enhanced with glutamate modulation via CDPPB treatment. To model THC and alcohol dependency, rats were exposed to 2 daily THC vapor for 5 days, followed by a chronic intermittent ethanol exposure (CIE) for 9hr/day for 10 days. Next, animals underwent a contextual fear conditioning paradigm where they learned to associate contextual and auditory cues with a mild foot-shock (0.75mA). Animals were then exposed to an extinction procedure that involved presentation of cues with no shock. Twenty minutes prior to each extinction session, rats received a subcutaneous injection of CDPPB (30mg/kg) or saline. The amount of time the rats remained still (freezing) during the tone was used as a measure of fear-related behavior. Our data supports our hypothesis that THC+CIE exposure increased deficits in fear extinction, and these deficits were recovered with CDPPB treatment. Therefore, deficits in extinction learning due to THC+CIE exposure can be prevented through modulation of mGlu5 function.
Start Time
16-4-2025 9:00 AM
End Time
16-4-2025 11:30 AM
Presentation Type
Poster
Presentation Category
Science, Technology and Engineering
Student Type
Graduate Student - Doctoral
Faculty Mentor
Justin Gass
Faculty Department
Biomedical Sciences
Behavioral Alterations in THC and Alcohol Co-Use: Insights into Fear Learning and Implications of mGlu5 Modulation
Cannabis is one of the most used illicit drugs, particularly in vulnerable populations such as veterans diagnosed with PTSD, adolescents, and those diagnosed with Alcohol Use Disorder. With increased legalization of recreational marijuana use across the United States, it is vital to understand the combined effects of THC and other commonly used drugs. Delta-9-tetrahydrocannabinol (THC), the psychoactive compound found in cannabis, has been shown to significantly impact both physiological and behavioral outcomes related to fear memory when used concomitantly with alcohol. Our lab aims to study these deficits and to investigate the benefits of mGlu5 modulation with CDPPB, a compound used to enhance extinction learning in models of drug dependence. The current study aimed to test the hypothesis that combined THC and alcohol exposure exacerbates fear learning, and extinction of fear can be enhanced with glutamate modulation via CDPPB treatment. To model THC and alcohol dependency, rats were exposed to 2 daily THC vapor for 5 days, followed by a chronic intermittent ethanol exposure (CIE) for 9hr/day for 10 days. Next, animals underwent a contextual fear conditioning paradigm where they learned to associate contextual and auditory cues with a mild foot-shock (0.75mA). Animals were then exposed to an extinction procedure that involved presentation of cues with no shock. Twenty minutes prior to each extinction session, rats received a subcutaneous injection of CDPPB (30mg/kg) or saline. The amount of time the rats remained still (freezing) during the tone was used as a measure of fear-related behavior. Our data supports our hypothesis that THC+CIE exposure increased deficits in fear extinction, and these deficits were recovered with CDPPB treatment. Therefore, deficits in extinction learning due to THC+CIE exposure can be prevented through modulation of mGlu5 function.