UC Santa Barbara

This dissertation investigates how age of drinking onset and biological sex influence the affective and cognitive consequences that follow from a history of alcohol binge-drinking. Using a rodent model of voluntary binge-drinking, this research examines how a history of binge- drinking impacts withdrawal-induced negative affect, spatial and working memory, and protein expression through its effects on key brain regions involved in these processes. The findings suggest that binge-drinking during adolescence leads both to long-term cognitive deficits and increases in anxiety and depression-like behaviors in adulthood. As in the human population, female rodents in the present data exhibit earlier and more severe behavioral disturbances during alcohol withdrawal relative to males—underlining the urgent need for sex-specific approaches in managing alcohol use disorder. Additionally, this research explores how sex-specific chemosensory stimuli influence anxiety-related behaviors, providing insights into environmental and procedural factors modulating the manifestation of negative affect. A key finding includes the identification of sex-dependent variations in the modulation of marble-burying behavior in response to sex-related odors. Biochemical analyses reveal significant alterations in glutamate receptor expression and other neuropathological markers in the prefrontal cortex, entorhinal cortex, and amygdala, which may be implicated in the animals’ observed behavioral anomalies. These results suggest that early alcohol exposure disrupts normal brain development, resulting in long-lasting effects that may manifest in later life. Taken together, this research offers key insights into the complex effects of age and sex on the neurobiological and behavioral impacts of alcohol binge-drinking. More broadly, these results highlight the benefits of creating distinct interventions across age groups and sexes both for treating alcohol use disorder and managing its cognitive and affective consequences.