Alcohol Drinking Alters Stress Coping via Extended Amygdala Kappa Opioid Receptor Signaling in Male Mice

Abstract

Maladaptive responses to stress are a hallmark of alcohol use disorder, but the mechanisms that underlie this are not well characterized. Here we show that kappa opioid receptor (KOR) signaling in the bed nucleus of the stria terminalis (BNST) is a critical molecular substrate promoting a maladaptive behavioral phenotype following heavy alcohol drinking.Altered responses to an innate stressor were associated with enhanced PFC-driven excitation of prodynorphin-containing neurons in the BNST during protracted withdrawal from intermittent alcohol drinking. These findings suggest that corticolimbic connectivity may underlie impaired stress-coping during protracted withdrawal from heavy drinking and represents a target of potential therapeutic mediation.BNST PDYN alcohol-induced stress deficit 2 Author ContributionsLSH, SN, CS, EK, and RC performed and analyzed behavioral tests. LSH, MEF, and OH provided support for and analyzed the fiber photometry experiments. LSH, SN, MMP, and DP assisted with electrophysiology experiments. WY and KB provided additional technical expertise. LSH and TLK conceptualized, designed the study, and wrote the manuscript.

Absence of effects of intermittent access to alcohol on negative affective and anxiety-like behaviors in male and female C57BL/6J mice

“…In this line, a recent report in male C57BL/6J mice exposed to a daily "binge-like" vapor exposure shows a lasting increase in impulsive-like behavior in the 5choice serial reaction time task (Starski, et al 2020). Also reminiscent of behavioral disinhibition, recent studies in male mice drinking in the IAA model showed increased aggressivity (Hwa, et al 2015) a maladaptive response to a predator odor in IAA drinking mice (Hwa, et al 2019). Albeit hard to interpret, the higher average velocity observed in male drinkers compared to water drinking controls on the EZM in our study could hint at a subtle effect of alcohol that affects male and female mice differently.…”