Abstract
Rationale
Alcohol and nicotine co-dependence is common in humans, and nicotine increases alcohol drinking in humans without alcohol use disorder (AUD). Nevertheless, there is little basic research on the interactions between the reinforcing effects of these two drugs.
Objectives
The aim of this study was to investigate the effects of chronic nicotine injections on oral alcohol self-administration in alcohol non-dependent rats.
Methods
After stable alcohol self-administration was reached (baseline) and a period without alcohol access, adult male rats were treated with chronic nicotine or saline injections for 105 days during which time they were tested intermittently for alcohol self-administration. There were 3 experimental groups: (1) saline, rats treated with saline for 105 days; (2) early nicotine, rats treated with nicotine for 70 days, and then with saline for 35 days; and (3) late nicotine: rats treated with saline for 35 days, and then with nicotine for 70 days.
Results
Our results indicate that (1) chronic nicotine increases alcohol consumption regardless of whether exposure to alcohol was interrupted (early nicotine) or not (late nicotine) before the start of nicotine treatment, (2) the number of alcohol reinforcements correlates to blood-alcohol levels, and (3) alcohol self-administration rapidly decreases when nicotine is no longer available (early nicotine).
Conclusions
These discoveries may have clinical implications in social drinkers that use nicotine products, in that chronic nicotine can escalate alcohol drinking and cessation of nicotine exposure may decrease alcohol use.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Albanes D, Jones DY, Micozzi MS, Mattson ME (1987) Associations between smoking and body weight in the US population: analysis of NHANES II. Am J Public Health 77(4):439–444. https://doi.org/10.2105/ajph.77.4.439
Alén F, Gómez R, González-Cuevas G, Navarro M, López-Moreno JA (2009) Nicotine causes opposite effects on alcohol intake: evidence in an animal experimental model of abstinence and relapse from alcohol. Nicotine Tob Res 11(11):1304–1311. https://doi.org/10.1093/ntr/ntp139
Anthony JC, Echeagaray-Wagner F (2000) Epidemiologic analysis of alcohol and tobacco use. Alcohol Res Health 24(4):201–208
Avegno EM, Gilpin NW (2019) Inducing alcohol dependence in rats using chronic intermittent exposure to alcohol Vapor. Bio Protoc 9(9):e3222. https://doi.org/10.21769/BioProtoc.3222
Barrett SP, Tichauer M, Leyton M, Pihl RO (2006) Nicotine increases alcohol self-administration in non-dependent male smokers. Drug Alcohol Depend 81(2):197–204. https://doi.org/10.1016/j.drugalcdep.2005.06.009
Besheer J, Palmatier MI, Metschke DM, Bevins RA (2004) Nicotine as a signal for the presence or absence of sucrose reward: a Pavlovian drug appetitive conditioning preparation in rats. Psychopharmacology 172(1):108–117. https://doi.org/10.1007/s00213-003-1621-9
Bishop C, Parker GC, Coscina DV (2002) Nicotine and its withdrawal alter feeding induced by paraventricular hypothalamic injections of neuropeptide Y in Sprague-Dawley rats. Psychopharmacology 162(3):265–272. https://doi.org/10.1007/s00213-002-1101-7
Blomqvist O, Ericson M, Johnson DH, Engel JA, Söderpalm B (1996) Voluntary ethanol intake in the rat: effects of nicotinic acetylcholine receptor blockade or subchronic nicotine treatment. Eur J Pharmacol 314(3):257–267. https://doi.org/10.1016/s0014-2999(96)00583-3
Bobo JK (1992) Nicotine dependence and alcoholism epidemiology and treatment. J Psychoactive Drugs 24(2):123–129. https://doi.org/10.1080/02791072.1992.10471633
Britt JP, Bonci A (2013) Alcohol and tobacco: how smoking may promote excessive drinking. Neuron 79(3):406–407. https://doi.org/10.1016/j.neuron.2013.07.018
Clark A, Lindgren S, Brooks SP, Watson WP, Little HJ (2001) Chronic infusion of nicotine can increase operant self-administration of alcohol. Neuropharmacology 41(1):108–117. https://doi.org/10.1016/s0028-3908(01)00037-5
Cloutier S, Wahl K, Baker C, Newberry RC (2014) The social buffering effect of playful handling on responses to repeated intraperitoneal injections in laboratory rats. J Am Assoc Lab Anim Sci 53(2):168–173
Commissaris RL (1993) Techniques in the behavioral and neural sciences. Chapter 17: conflict behaviors as animal models for the study of anxiety. Edited by Frans van Haaren, 1993, vol. 10, pp 443–474. https://doi.org/10.1016/B978-0-444-81444-9.50022-5
DiFranza JR, Guerrera MP (1990) Alcoholism and smoking. J stud alcohol 51(2):130-135. https://doi.org/10.15288/jsa.1990.51.130
Doyon WM, Dong Y, Ostroumov A, Thomas AM, Zhang TA, Dani JA (2013) Nicotine decreases ethanol-induced dopamine signaling and increases self-administration via stress hormones. Neuron 79(3):530–540. https://doi.org/10.1016/j.neuron.2013.06.006
Elliott BM, Faraday MM, Phillips JM, Grunberg NE (2004) Effects of nicotine on elevated plus maze and locomotor activity in male and female adolescent and adult rats. Pharmacol Biochem Behav 77(1):21–28. https://doi.org/10.1016/j.pbb.2003.09.016
Grant BF, Hasin DS, Chou SP, Stinson FS, Dawson DA (2004) Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 61(11):1107–1115. https://doi.org/10.1001/archpsyc.61.11.1107
Gross J, Stitzer ML (1989) Nicotine replacement: ten-week effects on tobacco withdrawal symptoms. Psychopharmacology 98(3):334–341. https://doi.org/10.1007/BF00451684
Gulliver SB, Kamholz BW, Helstrom AW (2006) Smoking cessation and alcohol abstinence: what do the data tell us? Alcohol Res Health 29(3):208–212
Harrison EL, McKee SA (2008) Young adult non-daily smokers: patterns of alcohol and cigarette use. Addict Behav 33(5):668–674. https://doi.org/10.1016/j.addbeh.2007.11.012
Hauser SR, Deehan GA Jr, Toalston JE, Bell RL, McBride WJ, Rodd ZA (2014) Enhanced alcohol-seeking behavior by nicotine in the posterior ventral tegmental area of female alcohol-preferring (P) rats: modulation by serotonin-3 and nicotinic cholinergic receptors. Psychopharmacology 231(18):3745–3755. https://doi.org/10.1007/s00213-014-3508-3
Henniger MS, Spanagel R, Wigger A, Landgraf R, Hölter SM (2002) Alcohol self-administration in two rat lines selectively bred for extremes in anxiety-related behavior. Neuropsychopharmacology 26(6):729–736. https://doi.org/10.1016/S0893-133X(01)00408-0
Hogle JM, Kaye JT, Curtin JJ (2010) Nicotine withdrawal increases threat-induced anxiety but not fear: neuroadaptation in human addiction. Biol Psychiatry 68(8):719–725. https://doi.org/10.1016/j.biopsych.2010.06.003
Irvine EE, Cheeta S, File SE (2001a) Tolerance to nicotine's effects in the elevated plus-maze and increased anxiety during withdrawal. Pharmacol Biochem Behav 68(2):319–325. https://doi.org/10.1016/s0091-3057(00)00449-4
Irvine EE, Cheeta S, Marshall M, File SE (2001b) Different treatment regimens and the development of tolerance to nicotine's anxiogenic effects. Pharmacol Biochem Behav 68(4):769–776. https://doi.org/10.1016/s0091-3057(01)00469-5
Javadi-Paydar M, Kerr TM, Harvey EL, Cole M, Taffe MA (2019) Effects of nicotine and THC vapor inhalation administered by an electronic nicotine delivery system (ENDS) in male rats. Drug Alcohol Depend 198:54–62. https://doi.org/10.1016/j.drugalcdep.2019.01.027
Jordan CJ, Andersen SL (2017) Sensitive periods of substance abuse: early risk for the transition to dependence. Developmental cognitive neuroscience 25:29–44. https://doi.org/10.1016/j.dcn.2016.10.004
Kouri EM, McCarthy EM, Faust AH, Lukas SE (2004) Pretreatment with transdermal nicotine enhances some of ethanol's acute effects in men. Drug Alcohol Depend 75(1):55–65. https://doi.org/10.1016/j.drugalcdep.2004.01.011
Kutlu MG, Parikh V, Gould TJ (2015) Nicotine addiction and psychiatric disorders. Int Rev Neurobiol 124:171–208. https://doi.org/10.1016/bs.irn.2015.08.004
Lê AD, Corrigall WA, Harding JW, Juzytsch W, Li TK (2000) Involvement of nicotinic receptors in alcohol self-administration. Alcohol Clin Exp Res 24(2):155–163. https://doi.org/10.1111/j.1530-0277.2000.tb04585
Lê AD, Wang A, Harding S, Juzytsch W, Shaham Y (2003) Nicotine increases alcohol self-administration and reinstates alcohol seeking in rats. Psychopharmacology 168(1–2):216–221. https://doi.org/10.1007/s00213-002-1330-9
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(20):4019–4029. https://doi.org/10.1007/s00213-014-3541-2
Leão RM, Cruz FC, Vendruscolo LF, de Guglielmo G, Logrip ML, Planeta CS, Hope BT, Koob GF, George O (2015) Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking [published correction appears in J Neurosci 2015 Aug 5;35(31):11169]. J Neurosci 35(15):6241–6253. https://doi.org/10.1523/JNEUROSCI.3302-14.2015
LeCocq MR, Randall PA, Besheer J, Chaudhri N (2020) Considering drug-associated contexts in substance use disorders and treatment development. Neurotherapeutics 17(1):43–54. https://doi.org/10.1007/s13311-019-00824-2
Littleton J, Barron S, Prendergast M, Nixon SJ (2007) Smoking kills (alcoholics)! shouldn't we do something about it? Alcohol Alcohol 42(3):167–173. https://doi.org/10.1093/alcalc/agm019
López-Moreno JA, Trigo-Díaz JM, Rodríguez de Fonseca F, González Cuevas G, Gómez de Heras R, Crespo Galán I, Navarro M (2004) Nicotine in alcohol deprivation increases alcohol operant self-administration during reinstatement. Neuropharmacology 47(7):1036–1044. https://doi.org/10.1016/j.neuropharm.2004.08.002
Matta SG, Balfour DJ, Benowitz NL, Boyd RT, Buccafusco JJ, Caggiula AR, Craig CR, Collins AC, Damaj MI, Donny EC, Gardiner PS, Grady SR, Heberlein U, Leonard SS, Levin ED, Lukas RJ, Markou A, Marks MJ, McCallum SE, Parameswaran N, Perkins KA, Picciotto MR, Quik M, Rose JE, Rothenfluh A, Schafer WR, Stolerman IP, Tyndale RF, Wehner JM, Zirger JM (2007) Guidelines on nicotine dose selection for in vivo research. Psychopharmacology 190(3):269–319. https://doi.org/10.1007/s00213-006-0441-0
McDermott MS, Marteau TM, Hollands GJ, Hankins M, Aveyard P (2013) Change in anxiety following successful and unsuccessful attempts at smoking cessation: cohort study. Br J Psychiatry Jan 202(1):62–67. https://doi.org/10.1192/bjp.bp.112.114389
Miller NS, Gold MS (1998) Comorbid cigarette and alcohol addiction: epidemiology and treatment. J Addict Dis 17(1):55–66. https://doi.org/10.1300/J069v17n01_06
Morales-Mulia M (2019) Intra-accumbal orexin-1 receptor inhibition prevents the anxiolytic-like effect of ethanol and leads to increases in orexin-A content and receptor expression. Pharmacol Biochem Behav 185:172761. https://doi.org/10.1016/j.pbb.2019.172761
Morud J, Strandberg J, Andrén A, Ericson M, Söderpalm B, Adermark L (2018) Progressive modulation of accumbal neurotransmission and anxiety-like behavior following protracted nicotine withdrawal. Neuropharmacology 128:86–95. https://doi.org/10.1016/j.neuropharm.2017.10.002
Nadal R, Samson HH (1999) Operant ethanol self-administration after nicotine treatment and withdrawal. Alcohol 7(2):139–147. https://doi.org/10.1016/s0741-8329(98)00045-7
Novak A, Burgess ES, Clark M, Zvolensky MJ, Brown RA (2003) Anxiety sensitivity, self-reported motives for alcohol and nicotine use, and level of consumption. J Anxiety Disord 17(2):165–180. https://doi.org/10.1016/s0887-6185(02)00175-5
O'Hara P, Connett JE, Lee WW, Nides M, Murray R, Wise R (1998) Early and late weight gain following smoking cessation in the lung health study. Am J Epidemiol 148(9):821–830. https://doi.org/10.1093/oxfordjournals.aje.a009706
Olausson P, Ericson M, Löf E, Engel JA, Söderpalm B (2001) Nicotine-induced behavioral disinhibition and ethanol preference correlate after repeated nicotine treatment. Eur J Pharmacol 417(1–2):117–123. https://doi.org/10.1016/s0014-2999(01)00903-7
Ostroumov A, Dani JA (2018) Convergent neuronal plasticity and metaplasticity mechanisms of stress, nicotine, and alcohol. Annu Rev Pharmacol Toxicol 58:547–566. https://doi.org/10.1146/annurev-pharmtox-010617-052735
Ostroumov A, Thomas AM, Dani JA, Doyon WM (2015) Cigarettes and alcohol: the influence of nicotine on operant alcohol self-administration and the mesolimbic dopamine system. Biochem Pharmacol 97(4):550–557. https://doi.org/10.1016/j.bcp.2015.07.038
Parnell SE, West JR, Chen WJ (2006) Nicotine decreases blood alcohol concentrations in adult rats: a phenomenon potentially related to gastric function. Alcohol Clin Exp Res 30(8):1408–1413. https://doi.org/10.1111/j.1530-0277.2006.00168.x
Pennington ZT, Dong Z, Feng Y, et al. (2019) ezTrack: an open-source video analysis pipeline for the investigation of animal behavior. Sci Rep 9(1):19979. Published 2019 Dec 27. https://doi.org/10.1038/s41598-019-56408-9
Potthoff AD, Ellison G, Nelson L (1983) Ethanol intake increases during continuous administration of amphetamine and nicotine, but not several other drugs. Pharmacol Biochem Behav 18(4):489–493. https://doi.org/10.1016/0091-3057(83)90269-1
Roltsch EA, Baynes BB, Mayeux JP, Whitaker AM, Baiamonte BA, Gilpin NW (2014) Predator odor stress alters corticotropin-releasing factor-1 receptor (CRF1R)-dependent behaviors in rats. Neuropharmacology 79:83–89. https://doi.org/10.1016/j.neuropharm.2013.11.005
Sengupta P (2013) The laboratory rat: relating its age with human's. Int J Prev Med 4(6):624–630
Sharpe AL, Samson HH (2002) Repeated nicotine injections decrease operant ethanol self-administration. Alcohol 28(1):1–7. https://doi.org/10.1016/s0741-8329(02)00238-0
Stuart SA, Robinson ES (2015) Reducing the stress of drug administration: implications for the 3Rs. Sci Rep 5:14288. https://doi.org/10.1038/srep14288
Thompson BM, Barrett ST, Bevins RA (2019) Exploring the interoceptive stimulus effects of nicotine and varenicline. Pharmacol Biochem Behav 181:9–16. https://doi.org/10.1016/j.pbb.2019.04.001
Turner DM (1975) Influence of route of administration on metabolism of [14C] nicotine in four species. Xenobiotica 5(9):553–561. https://doi.org/10.3109/00498257509056125
Turner S, Mota N, Bolton J, Sareen J (2018) Self-medication with alcohol or drugs for mood and anxiety disorders: a narrative review of the epidemiological literature. Depress Anxiety 35(9):851–860. https://doi.org/10.1002/da.22771
Zarrindast MR, Aghamohammadi-Sereshki A, Rezayof A, Rostami P (2012) Nicotine-induced anxiogenic-like behaviours of rats in the elevated plus-maze: possible role of NMDA receptors of the central amygdala. J Psychopharmacol 26(4):555–563. https://doi.org/10.1177/0269881111412094
Funding
Funding for this award was provided by National Institute of Health (NIH) Award R01 AA023305 (NWG) and by the Merit Review Award #I01 BX003451 (NWG) from the United States (U.S.) Department of Veterans Affairs, Biomedical Laboratory Research and Development Service.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 35 kb)
Rights and permissions
About this article
Cite this article
Montanari, C., Secci, M.E., Driskell, A. et al. Chronic nicotine increases alcohol self-administration in adult male Wistar rats. Psychopharmacology 238, 201–213 (2021). https://doi.org/10.1007/s00213-020-05669-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-020-05669-8