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Unequal interactions between alcohol and nicotine co-consumption: suppression and enhancement of concurrent drug intake

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Abstract

Rationale

Alcohol and nicotine addiction are prevalent conditions that co-occur. Despite the prevalence of co-use, factors that influence the suppression and enhancement of concurrent alcohol and nicotine intake are largely unknown.

Objectives

Our goals were to assess how nicotine abstinence and availability influenced concurrent alcohol consumption and to determine the impact of quinine adulteration of alcohol on aversion-resistant alcohol consumption and concurrent nicotine consumption.

Methods

Male and female C57BL/6J mice voluntarily consumed unsweetened alcohol, nicotine, and water in a chronic 3-bottle choice procedure. In experiment 1, nicotine access was removed for 1 week and re-introduced the following week, while the alcohol and water bottles remained available at all times. In experiment 2, quinine (100–1000 μM) was added to the 20% alcohol bottle, while the nicotine and water bottles remained unaltered.

Results

In experiment 1, we found that alcohol consumption and preference were unaffected by the presence or absence of nicotine access in both male and female mice. In experiment 2a, we found that quinine temporarily suppressed alcohol intake and enhanced concurrent nicotine, but not water, preference in both male and female mice. In experiment 2b, chronic quinine suppression of alcohol intake increased nicotine consumption and preference in female mice without affecting water preference, whereas it increased water and nicotine preference in male mice.

Conclusions

Quinine suppression of alcohol consumption enhanced the preference for concurrent nicotine preference in male and female mice, suggesting that mice compensate for the quinine adulteration of alcohol by increasing their nicotine preference.

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References

  • Batel P, Pessione F, Maitre C, Rueff B (1995) Relationship between alcohol and tobacco dependencies among alcoholics who smoke. Addiction 90:977–980

    Article  CAS  PubMed  Google Scholar 

  • Blomqvist O, Ericson M, Johnson DH, Engel JA, Soderpalm B (1996) Voluntary ethanol intake in the rat: effects of nicotinic acetylcholine receptor blockade or subchronic nicotine treatment. Eur J Pharmacol 314:257–267

    Article  CAS  PubMed  Google Scholar 

  • de Bejczy A, Löf E, Walther L, Guterstam J, Hammarberg A, Asanovska G, Franck J, Isaksson A, Söderpalm B (2015) Varenicline for treatment of alcohol dependence: a randomized, placebo-controlled trial. Alcohol Clin Exp Res 39:2189–2199

    Article  CAS  PubMed  Google Scholar 

  • DeBaker MC, Robinson JM, Moen JK, Wickman K, Lee AM (2019) Differential patterns of alcohol and nicotine intake: combined alcohol and nicotine binge consumption behaviors in mice. Alcohol. https://doi.org/10.1016/j.alcohol.2019.09.006

  • Deehan GA, Hauser SR, Waeiss RA, Knight CP, Toalston JE, Truitt WA, McBride WJ, Rodd ZA (2015) Co-administration of ethanol and nicotine: the enduring alterations in the rewarding properties of nicotine and glutamate activity within the mesocorticolimbic system of female alcohol-preferring (P) rats. Psychopharmacology 232:4293–4302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Falk DE, Yi HY, Hiller-Sturmhofel S (2006) An epidemiologic analysis of co-occurring alcohol and tobacco use and disorders: findings from the National Epidemiologic Survey on Alcohol and Related Conditions. Alcohol Res Health 29:162–171

    PubMed  PubMed Central  Google Scholar 

  • Franck J, Jayaram-Lindström N (2013) Pharmacotherapy for alcohol dependence: status of current treatments. Curr Opin Neurobiol 23:692–699

    Article  CAS  PubMed  Google Scholar 

  • Fucito LM, Park A, Gulliver SB, Mattson ME, Gueorguieva RV, O’Malley SS (2012) Cigarette smoking predicts differential benefit from naltrexone for alcohol dependence. Biol Psychiatry 72:832–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heffner JL, Mingione C, Blom TJ, Anthenelli RM (2011) Smoking history, nicotine dependence, and changes in craving and mood during short-term smoking abstinence in alcohol dependent vs. control smokers. Addict Behav 36:244–247

    Article  PubMed  Google Scholar 

  • Hendrickson LM, Zhao-Shea R, Tapper AR (2009) Modulation of ethanol drinking-in-the-dark by mecamylamine and nicotinic acetylcholine receptor agonists in C57BL/6J mice. Psychopharmacology 204:563–572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hopf FW, Lesscher HM (2014) Rodent models for compulsive alcohol intake. Alcohol 48:253–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hopf FW, Chang SJ, Sparta DR, Bowers MS, Bonci A (2010) Motivation for alcohol becomes resistant to quinine adulteration after 3 to 4 months of intermittent alcohol self-administration. Alcohol Clin Exp Res 34:1565–1573

    Article  PubMed  PubMed Central  Google Scholar 

  • Hurt RD, Offord KP, Croghan IT, Gomez-Dahl L, Kottke TE, Morse RM, Melton LJ (1996) Mortality following inpatient addictions treatment. Role of tobacco use in a community-based cohort. JAMA 275:1097–1103

    Article  CAS  PubMed  Google Scholar 

  • Hwa LS, Chu A, Levinson SA, Kayyali TM, DeBold JF, Miczek KA (2011) Persistent escalation of alcohol drinking in C57BL/6J mice with intermittent access to 20% ethanol. Alcohol Clin Exp Res 35:1938–1947

    Article  PubMed  PubMed Central  Google Scholar 

  • Kahler CW, Cioe PA, Tzilos GK, Spillane NS, Leggio L, Ramsey SE, Brown RA, O’Malley SS (2017) A double-blind randomized placebo-controlled trial of oral naltrexone for heavy-drinking smokers seeking smoking cessation treatment. Alcohol Clin Exp Res 41:1201–1211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamens HM, Andersen J, Picciotto MR (2010) Modulation of ethanol consumption by genetic and pharmacological manipulation of nicotinic acetylcholine receptors in mice. Psychopharmacology 4:253–260

    Google Scholar 

  • Kamens HM, Hoft NR, Cox RJ, Miyamoto JH, Ehringer MA (2012) The alpha6 nicotinic acetylcholine receptor subunit influences ethanol-induced sedation. Alcohol 46:463–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • King A, McNamara P, Conrad M, Cao D (2009) Alcohol-induced increases in smoking behavior for nicotinized and denicotinized cigarettes in men and women. Psychopharmacology 207:107–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lê AD, Corrigall WA, Harding JW, Juzytsch W, Li TK (2000) Involvement of nicotinic receptors in alcohol self-administration. Alcohol Clin Exp Res 24:155–163

    Article  PubMed  Google Scholar 

  • Lê AD, Wang A, Harding S, Juzytsch W, Shaham Y (2003) Nicotine increases alcohol self-administration and reinstates alcohol seeking in rats. Psychopharmacology 168:216–221

    Article  CAS  PubMed  Google Scholar 

  • Lê AD, Lo S, Harding S, Juzytsch W, Marinelli PW, Funk D (2010) Coadministration of intravenous nicotine and oral alcohol in rats. Psychopharmacology 208:475–486

    Article  CAS  PubMed  Google Scholar 

  • Lê AD, Funk D, Lo S, Coen K (2014) Operant self-administration of alcohol and nicotine in a preclinical model of co-abuse. Psychopharmacology 231:4019–4029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee AM, Messing RO (2011) Protein kinase C epsilon modulates nicotine consumption and dopamine reward signals in the nucleus accumbens. Proc Natl Acad Sci U S A 108:16080–16085

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee AM, Zou ME, Lim JP, Stecher J, McMahon T, Messing RO (2014) Deletion of Prkcz increases intermittent ethanol consumption in mice. Alcohol Clin Exp Res 38:170–178

    Article  CAS  PubMed  Google Scholar 

  • Leeman RF, Huffman CJ, O’Malley SS (2007) Alcohol history and smoking cessation in nicotine replacement therapy, bupropion sustained release and varenicline trials: a review. Alcohol Alcohol 42:196–206

    Article  PubMed  Google Scholar 

  • Leeman RF, McKee SA, Toll BA, Krishnan-Sarin S, Cooney JL, Makuch RW, O’Malley SS (2008) Risk factors for treatment failure in smokers: relationship to alcohol use and to lifetime history of an alcohol use disorder. Nicotine Tob Res 10:1793–1809

    Article  CAS  PubMed  Google Scholar 

  • Lei K, Wegner SA, Yu JH, Simms JA, Hopf FW (2016) A single alcohol drinking session is sufficient to enable subsequent aversion-resistant consumption in mice. Alcohol 55:9–16

    Article  PubMed  PubMed Central  Google Scholar 

  • Lesscher HM, van Kerkhof LW, Vanderschuren LJ (2010) Inflexible and indifferent alcohol drinking in male mice. Alcohol Clin Exp Res 34:1219–1225

    CAS  PubMed  Google Scholar 

  • Litten RZ, Ryan ML, Fertig JB, Falk DE, Johnson B, Dunn KE, Green AI, Pettinati HM, Ciraulo DA, Sarid-Segal O, Kampman K, Brunette MF, Strain EC, Tiouririne NA, Ransom J, Scott C, Stout R (2013) A double-blind, placebo-controlled trial assessing the efficacy of varenicline tartrate for alcohol dependence. J Addict Med 7:277–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Locklear LL, McDonald CG, Smith RF, Fryxell KJ (2012) Adult mice voluntarily progress to nicotine dependence in an oral self-selection assay. Neuropharmacology 63:582–592

    Article  CAS  PubMed  Google Scholar 

  • Maggio SE, Saunders MA, Baxter TA, Nixon K, Prendergast MA, Zheng G, Crooks P, Dwoskin LP, Slack RD, Newman AH, Bell RL, Bardo MT (2018) Effects of the nicotinic agonist varenicline, nicotinic antagonist r-bPiDI, and DAT inhibitor (R)-modafinil on co-use of ethanol and nicotine in female P rats. Psychopharmacology 235:1439–1453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marks JL, Hill EM, Pomerleau CS, Mudd SA, Blow FC (1997) Nicotine dependence and withdrawal in alcoholic and nonalcoholic ever-smokers. J Subst Abus Treat 14:521–527

    Article  CAS  Google Scholar 

  • Meliska CJ, Bartke A, McGlacken G, Jensen RA (1995) Ethanol, nicotine, amphetamine, and aspartame consumption and preferences in C57BL/6 and DBA/2 mice. Pharmacol Biochem Behav 50:619–626

    CAS  PubMed  Google Scholar 

  • Miller NS, Gold MS (1998) Comorbid cigarette and alcohol addiction: epidemiology and treatment. J Addict Dis 17:55–66

    Article  CAS  PubMed  Google Scholar 

  • Mitchell JM, Teague CH, Kayser AS, Bartlett SE, Fields HL (2012) Varenicline decreases alcohol consumption in heavy-drinking smokers. Psychopharmacology 223:299–306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Malley SS, Zweben A, Fucito LM, Wu R, Piepmeier ME, Ockert DM, Bold KW, Petrakis I, Muvvala S, Jatlow P, Gueorguieva R (2018) Effect of varenicline combined with medical management on alcohol use disorder with comorbid cigarette smoking: a randomized clinical trial. JAMA Psychiatry 75:129–138

    Article  PubMed  Google Scholar 

  • O’Rourke KY, Touchette JC, Hartell EC, Bade EJ, Lee AM (2016) Voluntary co-consumption of alcohol and nicotine: effects of abstinence, intermittency, and withdrawal in mice. Neuropharmacology 109:236–246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plebani JG, Lynch KG, Rennert L, Pettinati HM, O’Brien CP, Kampman KM (2013) Results from a pilot clinical trial of varenicline for the treatment of alcohol dependence. Drug Alcohol Depend 133:754–758

    Article  CAS  PubMed  Google Scholar 

  • Powers MS, Broderick HJ, Drenan RM, Chester JA (2013) Nicotinic acetylcholine receptors containing alpha6 subunits contribute to alcohol reward-related behaviours. Genes Brain Behav 12:543–553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rollema H, Shrikhande A, Ward KM, Tingley FD, Coe JW, O’Neill BT, Tseng E, Wang EQ, Mather RJ, Hurst RS, Williams KE, de Vries M, Cremers T, Bertrand S, Bertrand D (2010) Pre-clinical properties of the alpha4beta2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence. Br J Pharmacol 160:334–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simms JA, Steensland P, Medina B, Abernathy KE, Chandler LJ, Wise R, Bartlett SE (2008) Intermittent access to 20% ethanol induces high ethanol consumption in long-Evans and Wistar rats. Alcohol Clin Exp Res 32:1816–1823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith AM, Kelly RB, Chen WJ (2002) Chronic continuous nicotine exposure during periadolescence does not increase ethanol intake during adulthood in rats. Alcohol Clin Exp Res 26:976–979

    Article  CAS  PubMed  Google Scholar 

  • Sneddon EA, White RD, Radke AK (2019) Sex differences in binge-like and aversion-resistant alcohol drinking in C57BL/6J mice. Alcohol Clin Exp Res 43:243–249

    CAS  PubMed  Google Scholar 

  • Spanagel R, Hölter SM, Allingham K, Landgraf R, Zieglgänsberger W (1996) Acamprosate and alcohol: I. effects on alcohol intake following alcohol deprivation in the rat. Eur J Pharmacol 305:39–44

    Article  CAS  PubMed  Google Scholar 

  • Swan GE, Carmelli D, Cardon LR (1996) The consumption of tobacco, alcohol, and coffee in Caucasian male twins: a multivariate genetic analysis. J Subst Abus 8:19–31

    Article  CAS  Google Scholar 

  • Swan GE, Carmelli D, Cardon LR (1997) Heavy consumption of cigarettes, alcohol and coffee in male twins. J Stud Alcohol 58:182–190

    Article  CAS  PubMed  Google Scholar 

  • Tarren JR, Bartlett SE (2017) Alcohol and nicotine interactions: pre-clinical models of dependence. Am J Drug Alcohol Abuse 43:146–154

    Article  PubMed  Google Scholar 

  • Toll BA, White M, Wu R, Meandzija B, Jatlow P, Makuch R, O’Malley SS (2010) Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: a randomized trial. Drug Alcohol Depend 111:200–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toll BA, Cummings KM, O’Malley SS, Carlin-Menter S, McKee SA, Hyland A, Wu R, Hopkins J, Celestino P (2012) Tobacco quitlines need to assess and intervene with callers’ hazardous drinking. Alcohol Clin Exp Res 36:1653–1658

    Article  PubMed  PubMed Central  Google Scholar 

  • Touchette JC, Maertens JJ, Mason MM, O’Rourke KY, Lee AM (2018) The nicotinic receptor drug sazetidine-A reduces alcohol consumption in mice without affecting concurrent nicotine consumption. Neuropharmacology 133:63–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • True WR, Xian H, Scherrer JF, Madden PA, Bucholz KK, Heath AC, Eisen SA, Lyons MJ, Goldberg J, Tsuang M (1999) Common genetic vulnerability for nicotine and alcohol dependence in men. Arch Gen Psychiatry 56:655–661

    Article  CAS  PubMed  Google Scholar 

  • Truitt WA, Hauser SR, Deehan GA, Toalston JE, Wilden JA, Bell RL, McBride WJ, Rodd ZA (2015) Ethanol and nicotine interaction within the posterior ventral tegmental area in male and female alcohol-preferring rats: evidence of synergy and differential gene activation in the nucleus accumbens shell. Psychopharmacology 232:639–649

    Article  CAS  PubMed  Google Scholar 

  • Van Skike CE, Maggio SE, Reynolds AR, Casey EM, Bardo MT, Dwoskin LP, Prendergast MA, Nixon K (2016) Critical needs in drug discovery for cessation of alcohol and nicotine polysubstance abuse. Prog Neuro-Psychopharmacol Biol Psychiatry 65:269–287

    Article  CAS  Google Scholar 

  • Waeiss RA, Knight CP, Hauser SR, Pratt LA, McBride WJ, Rodd ZA (2019) Therapeutic challenges for concurrent ethanol and nicotine consumption: naltrexone and varenicline fail to alter simultaneous ethanol and nicotine intake by female alcohol-preferring (P) rats. Psychopharmacology 236:1887–1900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the National Institute of Health grants T32DA007234 (MCD, JKM), F31AA026782 (JKM), R01DA034696 (KW) and R01AA026598 (AML).

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Authors and Affiliations

  1. Department of Pharmacology, University of Minnesota, 312 Church Street SE, Minneapolis, MN, 55455, USA

    Margot C. DeBaker, Janna K. Moen, Jenna M. Robinson, Kevin Wickman & Anna M. Lee

  2. Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN, 55455, USA

    Margot C. DeBaker, Janna K. Moen, Kevin Wickman & Anna M. Lee

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  1. Margot C. DeBaker
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  2. Janna K. Moen
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  3. Jenna M. Robinson
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Correspondence to Anna M. Lee.

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DeBaker, M.C., Moen, J.K., Robinson, J.M. et al. Unequal interactions between alcohol and nicotine co-consumption: suppression and enhancement of concurrent drug intake. Psychopharmacology 237, 967–978 (2020). https://doi.org/10.1007/s00213-019-05426-6

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  • DOI: https://doi.org/10.1007/s00213-019-05426-6

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