Document Type

Thesis

Date of Award

Spring 4-25-2024

Degree Name

Integrative Neuroscience (BS)

Department

PSYCHOLOGY

First Advisor

Terrence Deak

Second Advisor

Marvin Diaz

Third Advisor

Melissa Morales

Abstract

Adolescence is characterized by many socio-emotional and neurobiological changes that often coincide with increased amounts of stress and the onset of alcohol use. Stress has been known to modulate alcohol intake, although the literature regarding this directionality is mixed. Both alcohol and stress can have lasting impacts on HPA axis activation (alterations in stress reactivity) and neuroimmune function (microglial sensitization). It has yet to be evaluated how concurrent ethanol and stress (recapitulated through oral corticosterone (CORT) administration) modulates alcohol intake and impacts later stress sensitivity and microglial sensitization. It was hypothesized that chronic concurrent ethanol and CORT drinking would (1) alter ethanol intake, such that the higher concentrations of CORT would increase ethanol intake the most; (2) blunt HPA axis activation in response to restraint; and (3) sensitize microglia in the PVN. A single bottle chronic intermittent ethanol and CORT drinking paradigm was performed with adolescent female Sprague-Dawley rats to determine the modulation of ethanol intake by concurrent ethanol and CORT drinking. Following the paradigm and a brief period of abstinence, a 30-minute restraint challenge was administered to all rats, followed by rapid collection of blood plasma to evaluate peak CORT levels for stress reactivity. Lastly, RT-PCR was used to detect differential expression of microglial-associated genes in the PVN to investigate microglial sensitization. The study revealed that the addition of 25 μg/mL CORT to 10% EtOH increases total ethanol intake. There were no changes in plasma CORT levels following restraint or microglial-associated gene expression (e.g., IL1-β & IL-6) in the PVN, displaying that no physiological changes occurred from the concurrent ethanol and CORT drinking paradigm. The results of this study implicate that low-level, intermittent HPA axis activation can increase adolescent susceptibility for alcohol use but does not impact physiological function.

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