Differential effects of ethanol on behavior and GABA_A receptor expression in adult zebrafish (Danio rerio) with alternative stress coping styles

Variation in stress responses between individuals are linked to factors ranging from stress coping styles to sensitivity of neurotransmitter systems. Many anxiolytic compounds (e.g. ethanol) can increase stressor engagement through modulation of neurotransmitter systems and are used to investigate stress response mechanisms. There are two alternative suites of correlated behavioral and physiological responses to stressors (stress coping styles) that differ in exploration tendencies: proactive and reactive stress coping styles. By chronically treating individuals differing in stress coping style with ethanol, a GABA-acting drug, we assessed the role of the GABAergic system on the behavioral stress response. Specifically, we investigated resulting changes in stress-related behavior (i.e. exploratory behavior) and whole-brain GABA_A receptor subunits (gabra1, gabra2, gabrd, & gabrg2) in response to a novelty stressor. We found that ethanol-treated proactive individuals showed lower stress-related behaviors than their reactive counterparts. Proactive individuals showed significantly higher expression of gabra1, gabra2, and gabrg2 compared to reactive individuals and ethanol treatment resulted in upregulation of gabra1 and gabrg2 in both stress coping styles. These results suggest that impacts of ethanol on stress-related behaviors vary by stress coping style and that expression of select GABA_A receptor subunits may be one of the underlying mechanisms.