Alcohol availability during withdrawal gates the impact of alcohol vapor exposure on responses to alcohol cues

M. J. Carpio, Runbo Gao, Erica Wooner, Christelle A. Cayton, Jocelyn M. Richard

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Rationale: Chronic intermittent ethanol (CIE) vapor inhalation is a widely used model of alcohol dependence, but the impact of CIE on cue-elicited alcohol seeking is poorly understood. Objective: Here, we assessed the effects of CIE on alcohol-seeking elicited by cues paired with alcohol before or after CIE vapor inhalation. Methods: In experiment 1, male and female Long-Evans rats were trained in a discriminative stimulus (DS) task, in which one auditory cue (the DS) predicts the availability of 15% ethanol and a control cue (the NS) predicts no ethanol. Rats then underwent CIE or served as controls. Subsets of each group received access to oral ethanol twice a week during acute withdrawal. After CIE, rats were presented with the DS and NS cues under extinction and retraining conditions to determine whether they would alter their responses to these cues. In experiment 2, rats underwent CIE prior to training in the DS task. Results: CIE enhanced behavioral responses to cues previously paired with alcohol, but only in rats that received access to alcohol during acute withdrawal. When CIE occurred before task training, male rats were slower to develop cue responses and less likely to enter the alcohol port, even though they had received alcohol during acute withdrawal. Conclusions: These results suggest that CIE vapor inhalation alone does not potentiate the motivational value of alcohol cues but that an increase in cue responses requires alcohol experience during acute withdrawal. Furthermore, under some conditions, CIE may disrupt responses to alcohol-paired cues.

Original languageEnglish (US)
Pages (from-to)3103-3116
Number of pages14
Issue number10
StatePublished - Oct 2022

Bibliographical note

Funding Information:
This work was supported in part by the National Institutes of Health grants R00AA025384 and R01AA028770 to JMR.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.


  • Addiction
  • Alcohol dependence
  • Cues
  • Rat
  • Sex differences
  • Withdrawal


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