Sex Differences in Avoidance Behavior and Neuroinflammation in a Comorbid Model of Posttraumatic Stress Disorder and Alcohol Use Disorder
Location
D.P. Culp Center Ballroom
Start Date
4-5-2024 9:00 AM
End Date
4-5-2024 11:30 AM
Poster Number
104
Name of Project's Faculty Sponsor
Justin Gass
Faculty Sponsor's Department
Biomedical Sciences
Competition Type
Competitive
Type
Poster Presentation
Presentation Category
Health
Abstract or Artist's Statement
Post-traumatic stress disorder (PTSD) is a debilitating disorder with a prevalence rate of approximately 6%. PTSD is commonly associated with alcohol use disorder (AUD). Of those diagnosed with PTSD, 30%-59% also suffer from AUD. Currently, there are limited effective treatment options for those suffering from comorbid PTSD/AUD. Previous research suggests that biological sex differentially impacts comorbid PTSD/AUD, however, the underlying mechanisms are enigmatic. Those with PTSD and AUD also tend to avoid environmental cues associated with the disorders. Avoidance and freezing are two distinct defensive responses to threats that display sex differences as well. Active avoidance behavior involves actively taking steps to prevent or mitigate a perceived threat, such as moving away from a source of danger, like avoiding the location of the trauma. Freezing behavior, on the other hand, is a passive defensive response characterized by immobility, which is thought to reduce the likelihood of detection by predators, such as freezing in place when someone hears a sound associated with the trauma. The underlying mechanisms of avoidance and the apparent sex differences, however, are unknown. While some studies have investigated the neural mechanisms associated with avoidance fear responses, the impact that stress and chronic alcohol exposure have on avoidance behavior needs further investigation. Our lab recently found that in an animal model of comorbid PTSD/AUD, there are significant increases in neuroinflammation in the prelimbic (PrL), and infralimbic (IfL) cortices, and the hippocampus (HPC), all brain regions that are significantly involved in learning and memory. Both PTSD and AUD have been associated with increased proinflammatory markers in humans and animals, including tumor necrosis factor (TNF)- and interleukin (IL)-1 in plasma and the HPC and PrL. The purpose of this set of experiments was to utilize our rat model of PTSD/AUD comorbidity to assess changes in avoidance behaviors using the platform-mediated avoidance (PMA) paradigm and investigate brain region specific neuroinflammation. A comorbid PTSD/AUD rodent model was implemented in our lab using restraint stress (RS) and chronic intermittent ethanol exposure (CIE) in both male and female Wistar rats. This was followed by the PMA task to assess avoidance behavior where the rodents learned to avoid a tone-signaled footshock by stepping onto a nearby platform. In the experiments described, freezing was initially a common response to the tone that signaled a footshock, but as rats learned the avoidance task, freezing decreased. Importantly, a sex difference found that females displayed more active avoidance while the males displayed more passive avoidance by freezing. The neuroinflammation data was collected from the PrL, IfL and HPC of the brain tissue. TNF- and IL-1 enzyme linked-immunosorbent assays (ELISAs) were used to analyze the tissue. The neuroinflammation data indicated that males not exposed to RS or CIE showed higher levels of IL-1 than any other group. These results reveal that avoidance behavior strategies in comorbid PTSD/AUD are sex-dependent and neuroinflammation could be part of the pathology of comorbid PTSD/AUD.
Sex Differences in Avoidance Behavior and Neuroinflammation in a Comorbid Model of Posttraumatic Stress Disorder and Alcohol Use Disorder
D.P. Culp Center Ballroom
Post-traumatic stress disorder (PTSD) is a debilitating disorder with a prevalence rate of approximately 6%. PTSD is commonly associated with alcohol use disorder (AUD). Of those diagnosed with PTSD, 30%-59% also suffer from AUD. Currently, there are limited effective treatment options for those suffering from comorbid PTSD/AUD. Previous research suggests that biological sex differentially impacts comorbid PTSD/AUD, however, the underlying mechanisms are enigmatic. Those with PTSD and AUD also tend to avoid environmental cues associated with the disorders. Avoidance and freezing are two distinct defensive responses to threats that display sex differences as well. Active avoidance behavior involves actively taking steps to prevent or mitigate a perceived threat, such as moving away from a source of danger, like avoiding the location of the trauma. Freezing behavior, on the other hand, is a passive defensive response characterized by immobility, which is thought to reduce the likelihood of detection by predators, such as freezing in place when someone hears a sound associated with the trauma. The underlying mechanisms of avoidance and the apparent sex differences, however, are unknown. While some studies have investigated the neural mechanisms associated with avoidance fear responses, the impact that stress and chronic alcohol exposure have on avoidance behavior needs further investigation. Our lab recently found that in an animal model of comorbid PTSD/AUD, there are significant increases in neuroinflammation in the prelimbic (PrL), and infralimbic (IfL) cortices, and the hippocampus (HPC), all brain regions that are significantly involved in learning and memory. Both PTSD and AUD have been associated with increased proinflammatory markers in humans and animals, including tumor necrosis factor (TNF)- and interleukin (IL)-1 in plasma and the HPC and PrL. The purpose of this set of experiments was to utilize our rat model of PTSD/AUD comorbidity to assess changes in avoidance behaviors using the platform-mediated avoidance (PMA) paradigm and investigate brain region specific neuroinflammation. A comorbid PTSD/AUD rodent model was implemented in our lab using restraint stress (RS) and chronic intermittent ethanol exposure (CIE) in both male and female Wistar rats. This was followed by the PMA task to assess avoidance behavior where the rodents learned to avoid a tone-signaled footshock by stepping onto a nearby platform. In the experiments described, freezing was initially a common response to the tone that signaled a footshock, but as rats learned the avoidance task, freezing decreased. Importantly, a sex difference found that females displayed more active avoidance while the males displayed more passive avoidance by freezing. The neuroinflammation data was collected from the PrL, IfL and HPC of the brain tissue. TNF- and IL-1 enzyme linked-immunosorbent assays (ELISAs) were used to analyze the tissue. The neuroinflammation data indicated that males not exposed to RS or CIE showed higher levels of IL-1 than any other group. These results reveal that avoidance behavior strategies in comorbid PTSD/AUD are sex-dependent and neuroinflammation could be part of the pathology of comorbid PTSD/AUD.