# Adolescent/young adult alcohol exposure and subsequent vulnerability to stress induced anxiety > **NIH VA IK2** · DURHAM VA MEDICAL CENTER · 2024 · — ## Abstract Adolescence is a critical period of neural maturation that lasts into the mid-20s in humans, ages during which most U.S. military enlistments occur. Heavy episodic drinking is highly prevalent in this age group, particularly among young military personnel. Recent evidence indicates Veterans that engaged in early adolescent binge drinking (initiation before age 14) have a higher prevalence of alcohol use disorders (AUD), substance use disorders, depression, and stress. Risks for later development of these affective disorders in Veterans can be further exacerbated by acute stressors, suggesting compounding mechanisms between stress and alcohol on affective networks. However, this relationship is poorly understood and understudied, despite its important translational implications for Veterans' health. Recent studies in both humans and animal models have shown that adolescent/young-adult intermittent ethanol (AIE) exposure results in enduring deficits in brain function and behavior that persist well into adulthood and possibly for the life of the individual. We, and others, have shown these enduring effects of AIE to include deficits in neural, glial, and neuroimmune functions in several brain regions that are known to drive anxiety-like and other affective behaviors. Our current preliminary data demonstrate that animals with a history of adolescent alcohol exposure are hypersensitive to the effects of stress, inducing anxiety-like behavior. Thus, adolescent/young adult alcohol exposure may alter limbic brain structures that predispose individuals to stress- induced affective dysregulation long after the ethanol exposure. This suggests that Veterans with a history of early heavy drinking may be at elevated risk for stress-induced affective disorders. Therefore, we propose three objectives investigating rodent behavior, markers of neurocircuitry, and synaptic function. First we will conduct rodent behavioral studies to evaluate the anxiety- and depressive-like behaviors caused by the combination of adolescent ethanol exposure and adult stress, their longevity, and possible pharmacological amelioration. We will assess the role for gabapentin (Neurontin) to reverse the anxiety phenotype induced by adolescent alcohol and adult stress and characterize the longevity of the adolescent ethanol exposure and adult stress phenotype by testing for anxiety-like and depressive-like behavior 3 or 9 weeks after the final stressor. The second aim of the project is to identify neural circuits and mechanisms underlying this phenotype. We propose to use transgenic Fos-LacZ rats, to assess unbiased whole-brain anxiety-induced activation and functional connectivity to identify novel circuits of interest involved in the etiology of the phenotype. We will investigate the chemogenetic inhibition of the mPFC and vHipp to attenuate the anxiety phenotype. We also propose to explore neuroimmune, neurogenesis and neurodegeneration markers, using immunohistochemistry, in the mPFC ... ## Key facts - **NIH application ID:** 10807393 - **Project number:** 1IK2BX006152-01A2 - **Recipient organization:** DURHAM VA MEDICAL CENTER - **Principal Investigator:** Kati Lynn Healey - **Activity code:** IK2 (R01, R21, SBIR, etc.) - **Funding institute:** VA - **Fiscal year:** 2024 - **Award amount:** — - **Award type:** 1 - **Project period:** 2024-05-01 → 2029-04-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10807393 ## Citation > US National Institutes of Health, RePORTER application 10807393, Adolescent/young adult alcohol exposure and subsequent vulnerability to stress induced anxiety (1IK2BX006152-01A2). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10807393. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*