Effects of ethanol, naltrexone, nicotine and varenicline in an ethanol and nicotine co-use model in Sprague-Dawley rats

Cassie M. Chandler, Sarah E. Maggio, Hui Peng, Kimberly Nixon, Michael T. Bardo

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Background: As alcohol and nicotine use disorders are entwined, it may be possible to develop a single medication to treat both. We previously developed a model for ethanol (EtOH) and nicotine co-use in female selectively bred alcohol-preferring (P) rats. To model co-use in a genetically diverse population, we adapted the model to outbred Sprague-Dawley rats of both sexes and assessed the effect of drug pretreatments. Methods: In phase 1, rats were trained in a 2-bottle choice between water and a sweetened or unsweetened EtOH solution in operant chambers. In phase 2, rats were trained in nicotine self-administration under an increasing fixed ratio (FR) schedule with 2 bottles containing water or saccharin-sweetened EtOH also available. In phase 3, rats were pretreated with EtOH (0.5, 1.5 g/kg), naltrexone (0.3 mg/kg), nicotine (0.2, 0.6 mg/kg), varenicline (3.0 mg/kg) or vehicle before the session. Results: Sweetening the EtOH solution was required to obtain pharmacologically relevant levels of consumption in Phase 1, with males showing increased sweetened EtOH preference compared to females. In Phase 2, increasing the FR requirement for nicotine decreased nicotine infusions, but increased EtOH consumption. In Phase 3, EtOH, naltrexone, and nicotine failed to alter EtOH consumption; however, varenicline decreased both EtOH and nicotine intake. Conclusions: The co-use model was successfully adapted to Sprague-Dawley rats by adding saccharin to the EtOH solution. In contrast to previous results in P rats, varenicline reduced both EtOH and nicotine intake, indicating it may be a useful monotherapy for co-use in a genetically diverse population.

Original languageEnglish
Article number107988
JournalDrug and Alcohol Dependence
StatePublished - Jul 1 2020

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health [grant numbers: T32 DA035200 , R01 AA025591 ]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2020 Elsevier B.V.


  • Co-use
  • Ethanol
  • Naltrexone
  • Nicotine
  • Sprague-Dawley rat
  • Varenicline

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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