Early life Stress and Social Isolation as a Two-Hit Model for Examining Extinction Learning in Fear and Motivational Contexts

Bishop, Christina

Undergraduate Honors Thesis

Early life Stress and Social Isolation as a Two-Hit Model for Examining Extinction Learning in Fear and Motivational Contexts Public Deposited

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Citations

Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/gm80hw78d

Abstract

An essential component of understanding mental health is uncovering individual risk factors increasing vulnerability to stress-related disorders. Stress can distinctly alter the developing brain, impacting the ability to respond appropriately to future stress and reward learning. Adulthood stress, through factors like social isolation, may impact behaviors related to motivation. These two factors, early life stress (ELS) and social isolation, critically interact; ELS leaves individuals particularly vulnerable to the effects of adulthood social isolation while social enrichment may ameliorate behavioral deficits demonstrated by ELS. Prior work from our lab using a brief wet bedding stressor on postnatal day 5 (P5) was sufficient to produce persistent fear in adults in a conditioned suppression paradigm (Bercum et al. 2021; 2023). However, the previous study did not compare sex differences, nor did they separately compare the effects of reward versus fear extinction. In our study, male and female pups were exposed to early life stress (ELS) from P2-P10 using a limited bedding approach and brief saturated bedding. We separated cohorts into either paired or isolated housing. In adulthood, we conducted a series of assays to examine the effects of ELS and socialization within-subject: (1) instrumental reward learning, (2) fear acquisition, (3) fear extinction, (4) fear renewal, (5) conditioned suppression, (6) reward extinction. We observed sex-related differences based on ELS exposure and/or socialization. During fear learning and extinction, female ELS rats showed elevated fear relative to female controls, while males in ELS and control groups were similar. In both sexes, socialized animals displayed unimpaired extinction learning while isolated animals demonstrated spontaneous recovery and heightened fear behavior. Our data suggest that experiencing ELS paired with social isolation may have distinct and sex-dependent impacts on adult vulnerability to stress disorders while socialization offers a rescuing effect.

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