Cassie M Chandler1, Sarah E Maggio1, Hui Peng2, Kimberly Nixon3, Michael T Bardo4. 1. Department of Psychology, University of Kentucky, 106 B, Kastle Hall, Lexington, KY 40536, USA. 2. Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA. 3. Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA. 4. Department of Psychology, University of Kentucky, 106 B, Kastle Hall, Lexington, KY 40536, USA. Electronic address: mbardo@uky.edu.
Abstract
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.
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.
Authors: H Rollema; L K Chambers; J W Coe; J Glowa; R S Hurst; L A Lebel; Y Lu; R S Mansbach; R J Mather; C C Rovetti; S B Sands; E Schaeffer; D W Schulz; F D Tingley; K E Williams Journal: Neuropharmacology Date: 2006-12-08 Impact factor: 5.250
Authors: Pia Steensland; Jeffrey A Simms; Joan Holgate; Jemma K Richards; Selena E Bartlett Journal: Proc Natl Acad Sci U S A Date: 2007-07-11 Impact factor: 11.205
Authors: Cassie M Chandler; Usman Hamid; Sarah E Maggio; Hui Peng; James R Pauly; Joshua Beckmann; Kimberly Nixon; Michael T Bardo Journal: Drug Alcohol Depend Date: 2022-01-11 Impact factor: 4.492