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UBC Theses and Dissertations

Effects of prenatal alcohol exposure on social behavior neurobiology in rats Holman, Parker J.


Estimates indicate a 1-5% prevalence of Fetal Alcohol Spectrum Disorders (FASD) among American children, making prenatal alcohol exposure (PAE) a leading cause of developmental disability in North America. Among the cognitive, physiological and behavioral impairments associated with PAE in the clinical/pre-clinical literature, lifelong social behavior deficits serve as a unifying feature across the entire spectrum. Impaired social behavior in individuals with FASD has widespread implications for function in other domains and may contribute to difficulties within school, social rejection, trouble with the law, and later mental health problems. Importantly, early-life adversity (ELA) can also modulate social behavior development, and individuals with PAE are more likely to experience ELA. However, few studies have assessed the interactive effects of these two insults on social behavior development. Maturational changes associated with adolescence have significant consequences for social behavior development, making adolescence a unique period of increased vulnerability to social behavior dysfunction. My dissertation research focuses on establishing a comprehensive neurobehavioral profile of adolescent social behavior in a rat model of PAE. Our assessments of play behavior, social preference and recognition memory, as well as central oxytocin and vasopressin systems, critical modulators of social behavior function, indicate PAE impairs adolescent social behavior – especially with increasing complexity of the social context – and behavioral impairments are associated with altered neural activity and development of the oxytocin/vasopressin systems. Specifically, we found that PAE disrupts sustained play bouts with unexposed playmates, impairs social recognition memory – particularly in males – and alters oxytocin receptor expression and neural activity (c-fos expression) in limbic and forebrain regions important for social behavior function. Moreover, ELA generally exacerbated and extended the effects of PAE, highlighting the ability of the early environment to mediate outcomes of PAE and power of animal models to interrogate this relationship. The relevance of the current research stems from the need for establishing a more specific social neurobehavioral profile that could support the development of strategies for earlier diagnoses and more targeted interventions for FASD. Taken together, our results highlight that PAE directly impacts multiple aspects of social behavior and its underlying neurobiology and identifies potential targets for therapeutic intervention.

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