The objective of the present study was to determine the effectiveness of the opioid antagonist naltrexone at reducing the consumption of EtOH and nicotine in female alcohol-preferring (P) rats. P rats have been selectively bred to have a genetic predisposition for alcohol abuse, which allows them to be used as an animal model of alcoholism. P rats readily self-administer i.v nicotine (Le et al., 2016), have EtOH consumption during adolescence that is similar to that seen in adulthood, and operantly respond for EtOH until they are impaired/intoxicated (Bell et al., 2006). Thus, P rats are a useful model for studying naltrexone’s effects on EtOH and nicotine co-use

Bardo, Michael T.

Bell, Richard L.

Hamid, Usman Z.

Maggio, Sarah E.

Nixon, Kimberly

Prendergast, Mark A.

Saunders, Meredith A.

English

University of Kentucky

University of KentuckyUKnowledgePosters-at-the-Capitol Presentations The Office of Undergraduate Research2019Effects of Naltrexone on Alcohol and Nicotine Usein Female P RatsUsman Z. HamidUniversity of Kentucky, usman.hamid@uky.eduSarah E. MaggioUniversity of Kentucky, sarah.maggio@uky.eduMeredith A. SaundersUniversity of Kentucky, meredith.saunders226@gmail.comKimberly NixonUniversity of Kentucky, kim-nixon@uky.eduMark A. PrendergastUniversity of Kentucky, mark.prendergast@uky.eduSee next page for additional authorsRight click to open a feedback form in a new tab to let us know how this document benefits you.Follow this and additional works at: https://uknowledge.uky.edu/capitol_presentPart of the Experimental Analysis of Behavior Commons, and the Substance Abuse andAddiction CommonsThis Article is brought to you for free and open access by the The Office of Undergraduate Research at UKnowledge. It has been accepted for inclusionin Posters-at-the-Capitol Presentations by an authorized administrator of UKnowledge. For more information, please contactUKnowledge@lsv.uky.edu.Recommended CitationHamid, Usman Z.; Maggio, Sarah E.; Saunders, Meredith A.; Nixon, Kimberly; Prendergast, Mark A.; Bell, Richard L.; and Bardo,Michael T., "Effects of Naltrexone on Alcohol and Nicotine Use in Female P Rats" (2019). Posters-at-the-Capitol Presentations. 2.https://uknowledge.uky.edu/capitol_present/2AuthorUsman Z. Hamid, Sarah E. Maggio, Meredith A. Saunders, Kimberly Nixon, Mark A. Prendergast, Richard L.Bell, and Michael T. BardoThis article is available at UKnowledge: https://uknowledge.uky.edu/capitol_present/2Effects of Naltrexone on Alcohol and Nicotine Use in Female P Rats Usman Z. Hamid1, Sarah E. Maggio1, Meredith A. Saunders1, Kimberly Nixon2, Mark A. Prendergast1, Richard L. Bell3, Michael T. Bardo11Department of Psychology, University of Kentucky2Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky3Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of MedicineLiterature CitedDiscussion ResultsBackground/IntroductionNaltrexoneResultsMethodResearch supported by NIH grants UL1 TR000117, P50 DA05312, T32 DA016176, R01AA025591, and U24AA015512.• Twelve adult female P rats• EtOH acclimation (3 days): water was removed from the home cage and rats were given a bottle of 20% EtOH.• Phase 1 & 2. Half the rats received naltrexone treatments during Phase 1, and half received treatments during Phase 2.In the EtOH-alone phase, naltrexone did not have any significant effect on EtOH orwater consumption. However, in the co-use phase, naltrexone dose-dependentlyreduced EtOH consumption; water consumption was also reduced, but only at thehighest dose (0.6 mg/kg). Also, in the co-use phase, naltrexone significantly reducedinactive lever presses for nicotine at the lowest dose (0.15 mg/kg), but it had no effecton active lever presses for nicotine. Thus, naltrexone is more effective in treating EtOHuse when tested in combination with nicotine rather than when tested alone.The present study used concurrent access to EtOH and nicotine, which has been usedin very few previous studies. It also measured choice for water (natural reward) andinactive lever presses (non-reinforced behavior) to determine if naltrexone had anyeffect on those behaviors. Because the highest dose of naltrexone (0.6 mg/kg) reducedwater drinking, we did not increase the test dose beyond that point. Further researchmust be conducted to find medications to treat the co-use of EtOH and nicotine.Future studies may involve counterbalancing the order in which EtOH alone andEtOH+nicotine co-use phases are administered. In addition, a higher FR schedule ofnicotine could be used (the highest ratio in the present study was FR30). A higher orlower dose of nicotine could also be used, or multiple doses could be used, in order todetermine if naltrexone would have significant effects on active lever presses. Finally,male P rats could be used as the test subjects in order to account for possible sexdifferences.According to the National Institutes on Health, although underage drinking and bingedrinking have declined in the past decade, alcohol (EtOH) is still the most commonlyabused substance in the United States (NCAAD, 2015) and worldwide (Falk et al., 2016).In addition, approximately 80% of people with an EtOH use disorder also use tobacco,which equates to more than 46 million co-abusers of EtOH and nicotine in the UnitedStates (Miller & Gold, 2008). Furthermore, the co-use of EtOH and nicotine increases thedifficulty of cessation of either substance (McKee & Weinberg, 2013). However, there iscurrently no single medication to treat the co-abuse of EtOH and nicotine, despite thetwo substances having similar mechanisms of action.The objective of the present study was to determine the effectiveness of the opioidantagonist naltrexone at reducing the consumption of EtOH and nicotine in femalealcohol-preferring (P) rats. P rats have been selectively bred to have a geneticpredisposition for alcohol abuse, which allows them to be used as an animal model ofalcoholism. P rats readily self-administer i.v nicotine (Le et al., 2016), have EtOHconsumption during adolescence that is similar to that seen in adulthood, and operantlyrespond for EtOH until they are impaired/intoxicated (Bell et al., 2006). Thus, P rats are auseful model for studying naltrexone’s effects on EtOH and nicotine co-use.Naltrexone has been FDA approved for alcohol use disorder based on its ability totreat alcohol dependence. Animal studies have shown that naltrexone decreases nicotineself-administration in rats (Ismayilova & Shoaib, 2010; Guy et al., 2014). In addition,naltrexone reduces EtOH self-administration in rats (Williams & Broadbridge, 2009) andalso reduces EtOH self-administration in rats given alternating access to either EtOH ornicotine (Le et al., 2014). These findings indicate that naltrexone has the potential toreduce the co-use of EtOH and nicotine.Modified Operant Chamber• Allowed rats concurrent access to i.v. nicotine (0.03 mg/kg/infusion) and oral EtOHand water (0 vs 15% EtOH).• Pressing the active lever provided rats with nicotine through a headmount/catheterconnected to the jugular vein.Figure 1: Effect of naltrexone pretreatment on EtOHconsumption in Phase 1 (EtOH-alone model). Figure 2: Effect of naltrexone pretreatment on water consumption in Phase 1.  Figure 6:  Effect of naltrexone pretreatment on inactive lever presses for nicotine in Phase 2. Figure 3: Effect of naltrexone pretreatment on EtOHconsumption in Phase 2 (concurrent access). Figure 5: Effect of naltrexone pretreatment on active lever presses for nicotine in Phase 2. Figure 4: Effect of naltrexone pretreatment on water consumption in Phase 2. Bell, R. L., Rodd, Z. A., Lumeng, L., Murphy, J. M., & McBride, W. J. (2006). The alcohol-preferring P rat and animal models of excessive alcohol drinking. Addiction Biology,11, 270-288. doi:10.1111/j.1369-1600.2006.00029.xFalk DE, Yi HY, Hiller-Sturmhofel S (2006) An epidemiologic analysis of co-occurringalcohol and tobacco use and disorders: findings from the National EpidemiologicSurvey on Alcohol and Related Conditions. Alcohol research & health: the journalof the National Institute on Alcohol Abuse and Alcoholism 29: 162-71.Guy, E. G., et al. (2014). "Examination of the effects of varenicline, bupropion, lorcaserin,or naltrexone on responding for conditioned reinforcement in nicotine-exposedrats." Behav Pharmacol 25(8): 775-783.Ismayilova, N. and M. Shoaib (2010). "Alteration of intravenous nicotine self-administration by opioid receptor agonist and antagonists in rats."Psychopharmacology (Berl) 210(2): 211-220.Lê, A. D., et al. (2014). "Operant self-administration of alcohol and nicotine in apreclinical model of co-abuse." Psychopharmacology (Berl) 231(20): 4019-4029.McKee SA, Weinberger AH (2013) How can we use our knowledge of alcohol-tobaccointeractions to reduce alcohol use? Annu Rev Clin Psychol 9: 649-74.Williams, K. L. and C. L. Broadbridge (2009). "Potency of naltrexone to reduce ethanolself-administration in rats is greater for subcutaneous versus intraperitonealinjection." Alcohol 43(2): 119-126.In Phase 1 (EtOH alone), naltrexone did not have any significant effect on EtOHconsumption or on water consumption (Figure 1 and 2). However, in Phase 2, naltrexonesignificantly reduced EtOH consumption at all three naltrexone doses tested (0.15, 0.3, and0.6 mg/kg), F(3, 18) = 1.57, p < 0.05 when compared to the vehicle control (Figure 3). Inaddition, naltrexone significantly reduced water consumption in Phase 2 but only at thehighest dose tested (0.6 mg/kg), F(3, 18) = 5.65, p < 0.05 (Figure 4). Also in Phase 2,naltrexone did not have any significant effect on active lever presses for nicotine (Figure 5).However, it did significantly reduce inactive lever presses for nicotine at the lowest dosetested (0.15 mg/kg), F(3, 18) = 3.38, p < 0.05 when compared to the vehicle control (Figure6).Phase 1 (Ethanol Access)Daily 60 min two-bottle choice sessions15% EtOH Bottle vs. Water BottlePhase 2 (Concurrent Access: EtOH + Nicotine)Food TrainingJugular Catheterization Surgery & Recovery Naltrexone pretreatments (0.15, 0.3, or 0.6 mg/kg) administered subcutaneously 15 min before test sessions EtOH and water bottles located on left wall of chamber.Active and inactive levers for nicotine self-administration located on right wall of chamber.DaysNicotine self-administration (0.03 mg/kg/infusion) trainingFR1 → FR3 → FR5 → FR8 → FR12 → FR20 → FR30 

Effects of Naltrexone on Alcohol and Nicotine Use in Female P Rats

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Effects of Naltrexone on Alcohol and Nicotine Use in Female P Rats

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