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Publication
Alcohol abstinence precipitates alcohol seeking and aversion-resistant intake in
association with increased BNST activity.
Authors Doyle MA, Yoon HJ, Altemus ME, Park AS, Troutman ME, Grunenkovaite L, Adank DN,
Edwards CM, Chetkovich NA, Hallal SD, Lantier L, Siciliano CA, Calipari ES,
Winder DG
Submitted By Submitted Externally on 7/6/2026
Status Published
Journal Molecular psychiatry
Year 2026
Date Published 6/3/2026
Volume : Pages Not Specified : Not Specified
PubMed Reference 42237002
Abstract Alcohol Use Disorder (AUD) is defined by a common diagnostic framework, yet
individuals show diverse drinking patterns and relapse vulnerabilities during
abstinence, reflecting neurobiological heterogeneity. The bed nucleus of the
stria terminalis (BNST) is well positioned to contribute to this variability. To
understand how BNST activity co-segregates with individual alcohol behavior
trajectories, we used the Structured Tracking of Alcohol Reinforcement (STAR)
operant task to phenotype C57BL/6J mice as high, low, or aversion-resistant
ethanol drinkers. During initial self-administration, dBNST cFos+ counts
correlated with intake, linking dBNST activation to operant drinking. Using in
vivo fiber photometry, we found that aversion-resistant drinkers displayed
elevated dBNST calcium transients during drinking bouts despite similar intake
across groups, consistent with heightened dBNST recruitment. Forced abstinence
uncovered prominent phenotype-specific adaptations, where ethanol seeking during
protracted, but not early, abstinence predicted aversion-resistant intake. High
and low drinkers reduced seeking behavior across abstinence, whereas
aversion-resistant drinkers persisted. Consistently, dBNST calcium transients
increased during protracted abstinence seeking only in aversion-resistant
drinkers, highlighting phenotype-specific plasticity. Comparing mice exposed to
abstinence versus only operant training showed that abstinence itself
potentiates aversion-resistant intake. Finally, these dBNST dynamics were
ethanol-specific, as saccharin drinking more closely reflected activity for high
drinkers. Together, these findings reveal that ethanol abstinence precipitates
ethanol seeking and aversion-resistant intake, associated with phenotypic dBNST
calcium dynamics. Because causality was not established, future studies are
needed to define mechanistic contributions of dBNST activity to phenotypic
behaviors. By uncovering how dBNST activity adapts in aversion-resistant
drinkers, this work offers insight into AUD heterogeneity.




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