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 disrupting stress-coping behavior 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 increased corticolimbic connectivity may underlie impaired stress-coping during protracted withdrawal from heavy drinking and represents a target of potential therapeutic mediation as well as a potential biomarker of negative outcomes.
Impact Statement Heavy alcohol drinking primes dynorphin / kappa opioid systems in the bed nucleus of the stria terminalis to alter stress coping responses.
Footnotes
Supplemental files updated, and full introduction and discussion included.