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Date of Presentation

5-8-2025

Document Type

Article

Department

Medicine

Faculty Mentor

Patrick J. Ronan, PhD

Second Advisor

Jennifer Agar

Third Advisor

Thomas P. Beresford, MD

Keywords

stress, neuroinflammation, learned helplessness, depression, rodent models

Subject Categories

Medicine and Health Sciences | Psychiatry

Abstract

Stress and neuroinflammation are increasingly recognized as interdependent processes that contribute to the development of psychiatric disorders. This study investigates the bidirectional relationship between stress exposure and neuroimmune activation, focusing on the expression of pro-inflammatory cytokines and behavioral outcomes in rodent models. Using the learned helplessness (LH) paradigm, the authors demonstrate that stress-induced neuroinflammation, particularly elevated IL-1β expression in the hypothalamus, is associated with susceptibility to maladaptive behaviors. The immunosuppressant cyclosporine A (CsA) was shown to attenuate stress-induced expression of neuroinflammatory markers, including IL-1β, IL-6, and CRF. Furthermore, direct intracerebroventricular administration of lipopolysaccharide (LPS), a TLR4 agonist, induced LH-like behavioral deficits in the absence of stress, confirming that neuroinflammation alone can mimic stress-induced behavioral phenotypes. These findings underscore a functional link between stress and neuroinflammatory signaling and suggest that targeting neuroimmune pathways may offer therapeutic potential for stress-related disorders such as depression, PTSD, and alcohol use disorder.

Effects of Calcineurin Mediated Immunosuppressant Cyclosporine on Binge Alcohol Drinking and Stress Responsivity

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