Alcohol drinking alters stress response to predator odor via bnst kappa opioid receptor signaling in male mice

Lara S. Hwa, Sofia Neira, Meghan E. Flanigan, Christina M. Stanhope, Melanie M. Pina, Dipanwita Pati, Olivia J. Hon, Waylin Yu, Emily Kokush, Rachel Calloway, Kristen Boyt, Thomas L. Kash

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 signaling in the bed nucleus of the stria terminalis (BNST) is a critical molecular substrate underlying abnormal stress responses to predator odor following heavy alcohol drinking. Exposure to predator odor during protracted withdrawal from intermittent alcohol drinking resulted in enhanced prefrontal cortex (PFC)-driven excitation of prodynorphin-containing neurons in the BNST. Furthermore, deletion of prodynorphin in the BNST and chemogenetic inhibition of the PFC-BNST pathway restored abnormal responses to predator odor in alcohol-exposed mice. These findings suggest that increased corticolimbic drive may promote abnormal stress behavioral responses to predator odor during protracted withdrawal. Various nodes of this PFC-BNST dynorphin-related circuit may serve as potential targets for potential therapeutic mediation as well as biomarkers of negative responses to stress following heavy alcohol drinking.

Original languageEnglish
Pages (from-to)1-53
Number of pages53
JournaleLife
Volume9
DOIs
StatePublished - Jul 2020
Externally publishedYes

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