Online

Laprade, Kathryn Anne

Pharmacology

2023

M.S.

Alcohol use disorder (AUD) has wide reaching impacts, both in the United States and globally. Annually, AUD accounts for over 2 million deaths and is the leading disease risk among those ages 25 to 49. In the United States, the effects of AUD are felt on a nuclear family and larger community level. A 2017 statistic reported that approximately 10.5% of children resided with a parent who had AUD. AUD also has large mental health impacts, with alcohol use being involved in an estimated 21% of suicides. The onset of the COVID-19 pandemic brought about traumatic instances of stress, mandated self-isolation, and unique alcohol-purchasing options. Moreover, the U.S. sees an average of 10,000 alcohol related driving fatalities annually, with 2021 being slightly above average at 13,384 alcohol-impaired driving fatalities. To date, COVID-19, stress, isolation, and correlated alcohol use patterns have been well reported on. Overall, the United States witnessed increased alcohol sales and consumption early in the pandemic, concurrent with many stay-at-home mandates. Literature suggests that impactful instances of stress as well as social isolation may have led to these early increases in alcohol consumption. Despite this growing literature, how alcohol consumption is driven by adverse life experiences combined with social isolation remains poorly understood due to challenges in developing models that capture this complex interaction. A primary goal of this thesis was to evaluate the ability of social isolation to modulate alcohol consumption following an adverse event. To accomplish this, I employed a well-characterized, repeated foot shock (adverse event) combined with chronic single or paired housing conditions to model social isolation. The interaction between housing condition and foot shock on ethanol consumption was explored using an established binge-drinking model, Drinking in the Dark (DID). I hypothesized that the combination of isolation and experience of repeated foot shock would lead to the highest levels of alcohol consumption as compared to paired and control groups. During DID, an effect of shock was seen in female mice only, with shocked mice consuming significantly more alcohol than not shocked. This sex effect remained through the final day of the DID procedure with no significant effect of housing. The shock effect in females seemed to dissipate by end of the DID procedure. A final day of 4-hour ethanol access following exposure to a fear-extinction paradigm for all groups revealed a significant effect of shock in males only, with not-shocked males drinking significantly more than shocked counterparts. Though results from this model did not mimic the rise in drinking levels as seen correlated with social isolation during the COVID-19 pandemic, it has bridged a current gap in combination adverse event and social isolation animal models. Results from this study also surfaced some interesting sex differences that could use further studying. Insight from this study will allow for experimental alteration and refinement to better address this current model gap. Future directions of this model include alteration of the shock paradigm, alterations in housing nature, and possible introduction of previous-alcohol-exposure.