# A Role for IL-1Beta in Ethanol Withdrawal-Induced Increase of PTSD-Like Phenotype > **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $184,656 ## Abstract Project Summary/Abstract Individuals that have been exposed to a traumatic event are at risk for developing a set of symptoms known as post-traumatic stress disorder (PTSD). Evidence suggests that there is a high comorbidity between PTSD and alcohol use disorders (AUDs), with a three-fold increased risk for experiencing an AUD in sufferers of PTSD. While it is generally thought PTSD proceeds, and is a risk factor for, AUDs, there is also evidence that a prior history of AUDs may leave individuals biologically more vulnerable to the impact of severe stress and thus more likely to develop PTSD. Despite converging evidence of co-morbidity between PTSD and AUDs, our understanding of the underlying neuronal substrates mediating these comorbid disorders, as well as available pharmaceutical treatments, are limited. This application brings together a team of investigators to address this scientific question in a convergent manner with the expertise of the neural immune mechanisms that underlie PTSD-like behavior (Lysle), the neurobiology of excessive alcohol (ethanol) intake (Thiele), and the understanding of astrocyte physiology (Reissner). Interestingly, a comparison of the present team’s research suggests that common overlapping neuroimmune mechanisms may underlie the development of each pathology. Dr. Lysle has discovered that severe stress induces a time-dependent increase in dorsal hippocampal (DH) interleukin-1β (IL-1β), and that directly blocking IL-1 signaling in the DH after severe stress (repeated unpredictable foot shock) prevents stress-enhanced fear learning (SEFL), an animal model of PTSD. Consistently, the present research team has found that withdrawal following chronic ethanol exposure increases hippocampal IL-1β mRNA, and a recent collaborative pilot project between the research team revealed that ethanol withdrawal potentiates the magnitude of SEFL. These observations support our overarching hypothesis, that hippocampal IL-1β represents a cellular mechanism for exacerbated stress response in alcohol- withdrawn/dependent individuals. Specific Aim 1 will test the hypothesis that withdrawal-induced potentiation of SEFL is associated with (A) a potentiation of IL-1β signaling specifically in astrocytes that correlates with the magnitude of SEFL, (B) pharmacological blockade of DH IL-1R during withdrawal will protect against withdrawal- induced potentiation of PTSD-like phenotypes, and (C) that DH-infusion of exogenous IL-1β will substitute for the effects of ethanol withdrawal. Specific Aim 2 will test the hypothesis that changes in the morphometric properties of astrocytes, and/or alterations of astrocyte/neuron interactions, correlate with increased astrocyte IL-1β levels stemming from ethanol withdrawal and the severe stress used in SEFL. The studies proposed here are appropriate for the R21 grant mechanism because they are high-reward, potentially filling a gap in our understanding of the role that astrocyte-derived cytokines play in ... ## Key facts - **NIH application ID:** 10079448 - **Project number:** 5R21AA027463-02 - **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL - **Principal Investigator:** DONALD T LYSLE - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $184,656 - **Award type:** 5 - **Project period:** 2020-01-03 → 2022-12-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10079448 ## Citation > US National Institutes of Health, RePORTER application 10079448, A Role for IL-1Beta in Ethanol Withdrawal-Induced Increase of PTSD-Like Phenotype (5R21AA027463-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10079448. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*