Blast exposure via detonation of explosives results in symptoms such as mild traumatic brain injury, post-traumatic stress disorder, and chronic pain, serving as a major source of trauma for service members, Veterans, and civilian bystanders. These effects characterize the polytrauma clinical triad and pose a risk factor for increased substance use and substance use disorder (SUD). This polytrauma exposure yields diverse symptom trajectories. To understand the interactions between polytrauma and SUD risk, we use a rodent model that utilizes custom, in-house-built polysubstance self-administration chambers, Socially Integrated Polysubstance (SIP) cages, to measure water, alcohol, and fentanyl intake. Two types of tracking are used to monitor drinking: Radio Frequency Identification (RFID) tracking and the volumetric drinking monitor, and these combined tell us which mouse drinks what liquid for a variable period of time. These SIP cages have the advantage to study both voluntary drinking habits and preferences as well as the effect of group housing on these patterns. For this project, we used 69 C57Bl/6 male and female mice aged 9 weeks on arrival. These mice were then single or group-housed in the SIP cages for 9 days to monitor drinking patterns. Testing multiple substances at once can give us valuable insight into substance preference and polysubstance use, making it more representative of the human experience. These mice had behavioral testing before entrance into the SIP cages, and we will explore different methods to characterize these drinking and anxiety subgroups that emerge. In addition, we plan to look at sex differences and how that changes substance use and preference. These factors combined will give valuable insight into classifying substance use that can lead to more optimized treatment for Veterans with polytrauma.

Veterans and Servicemembers experience trauma and chronic stress that lead to psychiatric disorders. Ample research has now demonstrated that blast exposure via detonation of high explosives on the battlefield can result in mild traumatic brain injury (mTBI) and it often occurs in combination with PTSD, depression, and addiction. Recently, Schindler Lab preliminarilly published that activation of dynorphin/kappa opioid receptor (KOR) system mediates stress/trauma-related dysphoria and anxiety-like outcomes. The expectation from this research project is that blast mTBI produces KOR activation to drive executive dysfunction and psychopathology and our aim is to understand the mechanisms underlying the adverse outcomes from blast-mTBI related to impaired executive functioning and determine the effect of blast trauma on the female and male population to understand sex as a biological variable. Prior to sham/blast exposure, mice will be injected with either vehicle (control) or norBNI that blocks activation of the KOR. Utilizing pneumatic shock tube and sophisticated operant paradigm in male and female mice, we modeled battle-field relevant open-field blast forces, detonation of high explosives to produce m-TBI and assessed various aspects of executive function (probability discounting, DRL, reversal learning, and progressive ratio) by monitoring the number and timing of lever presses and head entries into the food magazine of the operant chambers. Researching the chronic executive dysfunction mediated by blast-induced KOR activation during or immediately after repetitive blast exposure will contribute to understanding the underlying mechanisms regarding the effect of blast exposure on executive dysfunction for both females and males and the importance of timing on the effect to optimize further treatment options for veterans with an mTBI history and various psychiatric consequences. In the end, this research hopes to establish a novel understanding of mechanisms and treatment targets with experimental outcomes, giving rise to precision medicine approaches and endophenotype-specific treatment development.