CHARACTERIZING MOUSE BEHAVIORAL ADAPTATIONS AND THE ROLE OF PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS CORTICOTOPIN RELEASING HORMONE NEURONS IN ACUTE WITHDRAWAL FROM CHRONIC ALCOHOL CONSUMPTION

Alcohol use disorder (AUD) is a chronic relapsing condition that affects approximately 14.1 million Americans. Chronic alcohol use, with repeated withdrawal episodes, causes long lasting alterations to the body’s stress response system. While both alcohol and stress are known to modulate hormonal and subsequent behavioral responses to stressors, the mechanisms through which they interact are not fully known. One population of neurons critical for both behavioral and hormonal responses to stressors are the corticotropin releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVNCRH). In this dissertation, I examined stress related behavioral shifts and alterations to and function of PVNCRH neurons after chronic alcohol, using both in vivo and ex vivo measurements of PVNCRH neuron function. I test the hypothesis that chronic alcohol potentiates stress and the activity of PVNCRH neurons to alter active stress response behaviors. We find that a history of intermittent two-bottle choice alcohol consumption affects male and female mice behavior in sexually dimorphic ways in a low stress home-cage test of spontaneous natural behaviors, and in a visual threat looming disc assay that mimics an approaching predator. Male alcohol history mice also show increased anxiety/fear performances in a naturalistic foraging assay with a simulated predator threat. Ex-vivo electrophysiology experiments indicate alcohol history increases the excitability of PVNCRH neurons, with female mice being particularly affected by alcohol history. Accordingly, in-vivo chemogenetic inhibition of PVNCRH neurons restored stress related behaviors in the looming disc task in female alcohol history mice. The information gained from this dissertation can help with understanding the underlying mechanism between stress and alcohol interactions, which are implicated in the development of AUD and other conditions.