Advertisement

Psychopharmacology

, Volume 234, Issue 4, pp 727–738 | Cite as

Nicotine-induced enhancement of Pavlovian alcohol-seeking behavior in rats

  • Jean-Marie N. Maddux
  • Nadia ChaudhriEmail author
Original Investigation

Abstract

Rationale

Nicotine enhances responding elicited by Pavlovian cues that predict positive outcomes.

Objectives

We tested the hypothesis that nicotine acting at nicotinic acetylcholine receptors (nAChRs) would augment Pavlovian alcohol-seeking.

Methods

Male, Long-Evans rats with unrestricted access to food and water were acclimated to drinking 15% ethanol in their home cages and then given Pavlovian conditioning sessions in which each trial of a 15-s conditioned stimulus (CS, 12 trials/session) was paired with 0.2 ml of ethanol (unconditioned stimulus, US, 2.4 ml/session). Entries into a port where ethanol was delivered were used to assess conditioning. Control groups received explicitly unpaired trials of the CS and US. In experiment 1, systemic injections of saline (1 ml/kg) or nicotine (0.4 mg/kg, freebase) were administered before each session. In experiments 2 and 3, an identical regimen of saline or nicotine injections was administered before the start of Pavlovian conditioning sessions.

Results

All paired groups acquired conditioned port-entry responding to the CS, indicative of Pavlovian alcohol-seeking, whereas unpaired control group did not. Pre-session nicotine injections increased CS port-entries relative to saline, only in the paired group. This nicotine-induced enhancement of Pavlovian alcohol-seeking was blocked by pre-treatment with the nAChR antagonist mecamylamine. Prior exposure to nicotine did not influence the subsequent acquisition of Pavlovian alcohol-seeking.

Conclusions

These findings highlight for the first time that nicotine acting at nAChRs augments Pavlovian alcohol-seeking, specifically in non-restricted rats. Individuals who smoke and drink may thus be particularly susceptible to alcohol cues that could trigger further drinking.

Keywords

Pavlovian conditioned approach Ethanol Goal-tracking Mecamylamine 

Notes

Acknowledgements

A Nouveau Chercheur award (N.C.) from Fonds de la recherche du Québec—Santé (FRQS) funded this research. N.C. is the recipient of an FRQS Chercheur-Boursier Junior 1 award and a member of the Center for Studies in Behavioral Neurobiology/FRQS Groupe de recherche en neurobiologie comportementale (CSBN/GRNC). J-M.M. received funding from CSBN/GRNC, Concordia University and the Natural Sciences and Engineering Research Council (NSERC; N.C.). The authors would like to thank Stephen Cabilio for assistance with Med-PC programming and data extraction and Sabrina Heffernan, Angela Ortiz, Tracy Rothwell, and Chandra Srey for assistance with experiments.

Supplementary material

213_2016_4508_MOESM1_ESM.docx (149 kb)
ESM 1 (DOCX 149 kb).
213_2016_4508_MOESM2_ESM.docx (55 kb)
ESM 2 (DOCX 54 kb).
213_2016_4508_MOESM3_ESM.docx (54 kb)
ESM 3 (DOCX 54 kb).

References

  1. Bachteler D, Economidou D, Danysz W, Ciccocioppo R, Spanagel R (2005) The effects of acamprosate and neramexane on cue-induced reinstatement of ethanol-seeking behavior in rat. Neuropsychopharmacology 30:1104–1110CrossRefPubMedGoogle Scholar
  2. Bito-Onon JJ, Simms JA, Chatterjee S, Holgate J, Bartlett SE (2011) Varenicline, a partial agonist at neuronal nicotinic acetylcholine receptors, reduces nicotine-induced increases in 20% ethanol operant self-administration in Sprague-Dawley rats. Addict Biol 16:440–449CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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 314:257–267CrossRefPubMedGoogle Scholar
  4. Blum K, Liu Y, Shriner R, Gold MS (2011) Reward circuitry dopaminergic activation regulates food and drug craving behavior. Curr Pharm Des 17:1158–1167CrossRefPubMedGoogle Scholar
  5. Brown RW, Kolb B (2001) Nicotine sensitization increases dendritic length and spine density in the nucleus accumbens and cingulate cortex. Brain Res 899:94–100CrossRefPubMedGoogle Scholar
  6. Buisson B, Bertrand D (2001) Chronic exposure to nicotine upregulates the human (alpha)4(beta)2 nicotinic acetylcholine receptor function. J Neurosci 21:1819–1829PubMedGoogle Scholar
  7. Buisson B, Bertrand D (2002) Nicotine addiction: the possible role of functional upregulation. Trends Pharmacol Sci 23:130–136CrossRefPubMedGoogle Scholar
  8. Carnicella S, Ron D, Barak S (2014) Intermittent ethanol access schedule in rats as a preclinical model of alcohol abuse. Alcohol 48:243–252CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chaudhri N, Sahuque LL, Janak PH (2008) Context-induced relapse of conditioned behavioral responding to ethanol cues in rats. Biol Psychiatry 64:203–210CrossRefPubMedPubMedCentralGoogle Scholar
  10. Clemens KJ, Castino MR, Cornish JL, Goodchild AK, Holmes NM (2014) Behavioral and neural substrates of habit formation in rats intravenously self-administering nicotine. Neuropsychopharmacology 39:2584–2593CrossRefPubMedPubMedCentralGoogle Scholar
  11. Corbit LH, Janak PH (2007) Ethanol-associated cues produce general Pavlovian-instrumental transfer. Alcohol Clin Exp Res 31:766–774CrossRefPubMedGoogle Scholar
  12. Cunningham CL, Gremel CM, Groblewski PA (2006) Drug-induced conditioned place preference and aversion in mice. Nat Protoc 1:1662–1670CrossRefPubMedGoogle Scholar
  13. Dani JA, Harris RA (2005) Nicotine addiction and comorbidity with alcohol abuse and mental illness. Nat Neurosci 8:1465–1470CrossRefPubMedGoogle Scholar
  14. Di Chiara G, Acquas E, Tanda G, Cadoni C (1993) Drugs of abuse: biochemical surrogates of specific aspects of natural reward? Biochem Soc Symp 59:65–81PubMedGoogle Scholar
  15. Doyon WM, Dong Y, Ostroumov A, Thomas AM, Zhang TA, Dani JA (2013a) Nicotine decreases ethanol-induced dopamine signaling and increases self-administration via stress hormones. Neuron 79:530–540CrossRefPubMedPubMedCentralGoogle Scholar
  16. Doyon WM, Thomas AM, Ostroumov A, Dong Y, Dani JA (2013b) Potential substrates for nicotine and alcohol interactions: a focus on the mesocorticolimbic dopamine system. Biochem Pharmacol 86:1181–1193CrossRefPubMedPubMedCentralGoogle Scholar
  17. Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ (2002) Selected major risk factors and global and regional burden of disease. Lancet 360:1347–1360CrossRefPubMedGoogle Scholar
  18. Feduccia AA, Chatterjee S, Bartlett SE (2012) Neuronal nicotinic acetylcholine receptors: neuroplastic changes underlying alcohol and nicotine addictions. Front Mol Neurosci 5:83CrossRefPubMedPubMedCentralGoogle Scholar
  19. Field M, Duka T (2002) Cues paired with a low dose of alcohol acquire conditioned incentive properties in social drinkers. Psychopharmacology 159:325–334CrossRefPubMedGoogle Scholar
  20. Gallagher M, Graham PW, Holland PC (1990) The amygdala central nucleus and appetitive Pavlovian conditioning: lesions impair one class of conditioned behavior. J Neurosci 10:1906–1911PubMedGoogle Scholar
  21. Gauvin DV, Moore KR, Holloway FA (1993) Do rat strain differences in ethanol consumption reflect differences in ethanol sensitivity or the preparedness to learn? Alcohol 10:37–43CrossRefPubMedGoogle Scholar
  22. Glautier S, Clements K, White JA, Taylor C, Stolerman IP (1996) Alcohol and the reward value of cigarette smoking. Behav Pharmacol 7:144–154CrossRefPubMedGoogle Scholar
  23. Gotti C, Clementi F (2004) Neuronal nicotinic receptors: from structure to pathology. Prog Neurobiol 74:363–396CrossRefPubMedGoogle Scholar
  24. Govind AP, Vezina P, Green WN (2009) Nicotine-induced upregulation of nicotinic receptors: underlying mechanisms and relevance to nicotine addiction. Biochem Pharmacol 78:756–765CrossRefPubMedPubMedCentralGoogle Scholar
  25. Govind AP, Walsh H, Green WN (2012) Nicotine-induced upregulation of native neuronal nicotinic receptors is caused by multiple mechanisms. J Neurosci 32:2227–2238CrossRefPubMedPubMedCentralGoogle Scholar
  26. Greeley JD, Swift W, Prescott J, Heather N (1993) Reactivity to alcohol-related cues in heavy and light drinkers. J Stud Alcohol 54:359–368CrossRefPubMedGoogle Scholar
  27. Groblewski PA, Bax LS, Cunningham CL (2008) Reference-dose place conditioning with ethanol in mice: empirical and theoretical analysis. Psychopharmacology 201:97–106CrossRefPubMedPubMedCentralGoogle Scholar
  28. Gulliver SB, Rohsenow DJ, Colby SM, Dey AN, Abrams DB, Niaura RS, Monti PM (1995) Interrelationship of smoking and alcohol dependence, use and urges to use. J Stud Alcohol 56:202–206CrossRefPubMedGoogle Scholar
  29. Guy EG, Fletcher PJ (2013) Nicotine-induced enhancement of responding for conditioned reinforcement in rats: role of prior nicotine exposure and alpha4beta2 nicotinic receptors. Psychopharmacology 225:429–440CrossRefPubMedGoogle Scholar
  30. Guy EG, Fletcher PJ (2014) The effects of nicotine exposure during Pavlovian conditioning in rats on several measures of incentive motivation for a conditioned stimulus paired with water. Psychopharmacology 231:2261–2271CrossRefPubMedGoogle Scholar
  31. 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 231:3745–3755CrossRefPubMedPubMedCentralGoogle Scholar
  32. Hendrickson LM, Guildford MJ, Tapper AR (2013) Neuronal nicotinic acetylcholine receptors: common molecular substrates of nicotine and alcohol dependence. Front Psychiatry 4:29CrossRefPubMedPubMedCentralGoogle Scholar
  33. Holland PC, Gallagher M (1999) Amygdala circuitry in attentional and representational processes. Trends Cogn Sci 3:65–73CrossRefPubMedGoogle Scholar
  34. Janak PH, Chaudhri N (2010) The potent effect of environmental context on relapse to alcohol-seeking after extinction. Open Addict J 3:76–87CrossRefPubMedPubMedCentralGoogle Scholar
  35. John U, Hill A, Rumpf HJ, Hapke U, Meyer C (2003a) Alcohol high risk drinking, abuse and dependence among tobacco smoking medical care patients and the general population. Drug Alcohol Depend 69:189–195CrossRefPubMedGoogle Scholar
  36. John U, Meyer C, Rumpf HJ, Schumann A, Thyrian JR, Hapke U (2003b) Strength of the relationship between tobacco smoking, nicotine dependence and the severity of alcohol dependence syndrome criteria in a population-based sample. Alcohol Alcohol 38:606–612CrossRefPubMedGoogle Scholar
  37. Jones J, Raiff BR, Dallery J (2010) Nicotine’s enhancing effects on responding maintained by conditioned reinforcers are reduced by pretreatment with mecamylamine, but not hexamethonium. in rats Exp Clin Psychopharmacol 18:350–358CrossRefPubMedGoogle Scholar
  38. Katner SN, Magalong JG, Weiss F (1999) Reinstatement of alcohol-seeking behavior by drug-associated discriminative stimuli after prolonged extinction in the rat. Neuropsychopharmacology 20:471–479CrossRefPubMedGoogle Scholar
  39. Kaye H, Pearce JM (1984) The strength of the orienting response during Pavlovian conditioning. J Exp Psychol Anim Behav Process 10:90–109CrossRefPubMedGoogle Scholar
  40. Kelley AE, Schiltz CA, Landry CF (2005) Neural systems recruited by drug- and food-related cues: studies of gene activation in corticolimbic regions. Physiol Behav 86:11–14CrossRefPubMedGoogle Scholar
  41. Lajtha A, Sershen H (2010) Nicotine: alcohol reward interactions. Neurochem Res 35:1248–1258CrossRefPubMedGoogle Scholar
  42. Lê AD, Corrigall WA, Harding JW, Juzytsch W, Li TK (2000) Involvement of nicotinic receptors in alcohol self-administration. Alcohol Clin Exp Res 24:155–163CrossRefPubMedGoogle Scholar
  43. Lê AD, Wang A, Harding S, Juzytsch W, Shaham Y (2003) Nicotine increases alcohol self-administration and reinstates alcohol seeking in rats. Psychopharmacology 168:216–221CrossRefPubMedGoogle Scholar
  44. Liu X, Palmatier MI, Caggiula AR, Donny EC, Sved AF (2007) Reinforcement enhancing effect of nicotine and its attenuation by nicotinic antagonists in rats. Psychopharmacology 194:463–473CrossRefPubMedPubMedCentralGoogle Scholar
  45. Lof E, Olausson P, deBejczy A, Stomberg R, McIntosh JM, Taylor JR, Soderpalm B (2007) Nicotinic acetylcholine receptors in the ventral tegmental area mediate the dopamine activating and reinforcing properties of ethanol cues. Psychopharmacology 195:333–343CrossRefPubMedGoogle Scholar
  46. MacLeod JE, Vucovich MM, Bucci DJ (2010) Differential effects of nicotinic acetylcholine receptor stimulation on negative occasion setting. Behav Neurosci 124:656–661CrossRefPubMedPubMedCentralGoogle Scholar
  47. Mitchell JM, Teague CH, Kayser AS, Bartlett SE, Fields HL (2012) Varenicline decreases alcohol consumption in heavy-drinking smokers. Psychopharmacology 223:299–306CrossRefPubMedPubMedCentralGoogle Scholar
  48. Mugnaini M, Tessari M, Tarter G, Merlo Pich E, Chiamulera C, Bunnemann B (2002) Upregulation of [3H]methyllycaconitine binding sites following continuous infusion of nicotine, without changes of alpha7 or alpha6 subunit mRNA: an autoradiography and in situ hybridization study in rat brain. Eur J Neurosci 16:1633–1646CrossRefPubMedGoogle Scholar
  49. Nestler EJ (2005) Is there a common molecular pathway for addiction? Nat Neurosci 8:1445–1449CrossRefPubMedGoogle Scholar
  50. Olausson P, Ericson M, Lof E, Engel JA, Soderpalm B (2001) Nicotine-induced behavioral disinhibition and ethanol preference correlate after repeated nicotine treatment. Eur J Pharmacol 417:117–123CrossRefPubMedGoogle Scholar
  51. Olausson P, Jentsch JD, Taylor JR (2003) Repeated nicotine exposure enhances reward-related learning in the rat. Neuropsychopharmacology 28:1264–1271CrossRefPubMedGoogle Scholar
  52. Palmatier MI, Marks KR, Jones SA, Freeman KS, Wissman KM, Sheppard AB (2013) The effect of nicotine on sign-tracking and goal-tracking in a Pavlovian conditioned approach paradigm in rats. Psychopharmacology 226:247–259CrossRefPubMedGoogle Scholar
  53. Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (2013) Natural and drug rewards act on common neural plasticity mechanisms with DeltaFosB as a key mediator. J Neurosci 33:3434–3442CrossRefPubMedPubMedCentralGoogle Scholar
  54. 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 18:489–493CrossRefPubMedGoogle Scholar
  55. Rescorla RA, Wagner AR (1972) A theory of Pavlovian conditioning: variations in the effectiveness of reinforcement and nonreinforcement. In: Black A, Prokasy WF (eds) Classical conditioning II: current research and theory. Appleton-Century-Crofts, New York, NY, pp. 64–99Google Scholar
  56. Rezvani AH, Slade S, Wells C, Petro A, Lumeng L, Li TK, Xiao Y, Brown ML, Paige MA, McDowell BE, Rose JE, Kellar KJ, Levin ED (2010) Effects of sazetidine-A, a selective alpha4beta2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats. Psychopharmacology 211:161–174CrossRefPubMedPubMedCentralGoogle Scholar
  57. Robinson TE, Kolb B (2004) Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology 47(Suppl 1):33–46CrossRefPubMedGoogle Scholar
  58. Rohsenow DJ, Monti PM, Rubonis AV, Sirota AD, Niaura RS, Colby SM, Wunschel SM, Abrams DB (1994) Cue reactivity as a predictor of drinking among male alcoholics. J Consult Clin Psychol 62:620–626CrossRefPubMedGoogle Scholar
  59. Rohsenow DJ, Niaura RS, Childress AR, Abrams DB, Monti PM (1990) Cue reactivity in addictive behaviors: theoretical and treatment implications. Int J Addict 25:957–993CrossRefPubMedGoogle Scholar
  60. Room R (2004) Smoking and drinking as complementary behaviours. Biomed Pharmacother 58:111–115CrossRefPubMedGoogle Scholar
  61. Rose JE, Brauer LH, Behm FM, Cramblett M, Calkins K, Lawhon D (2002) Potentiation of nicotine reward by alcohol. Alcohol Clin Exp Res 26:1930–1931CrossRefPubMedGoogle Scholar
  62. Rose JE, Brauer LH, Behm FM, Cramblett M, Calkins K, Lawhon D (2004) Psychopharmacological interactions between nicotine and ethanol. Nicotine Tob Res 6:133–144CrossRefPubMedGoogle Scholar
  63. Schroeder BE, Binzak JM, Kelley AE (2001) A common profile of prefrontal cortical activation following exposure to nicotine- or chocolate-associated contextual cues. Neuroscience 105:535–545CrossRefPubMedGoogle Scholar
  64. Sharma R, Sahota P, Thakkar MM (2014) Nicotine administration in the cholinergic basal forebrain increases alcohol consumption in C57BL/6J mice. Alcohol Clin Exp Res 38:1315–1320CrossRefPubMedPubMedCentralGoogle Scholar
  65. Siddle DAT, Lipp OV (1997) Orienting, habituation, and information processing: the effects of omission, the role of expectancy, and the problem of dishabituation. In: Lang PJ, Simons RF, Balaban MT (eds) Attention and orienting: sensory and motivational processes. Lawrence Erlbaum Associates, Mahwah, NJ, pp 23–40Google Scholar
  66. 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 32:1816–1823CrossRefPubMedPubMedCentralGoogle Scholar
  67. Smith BR, Horan JT, Gaskin S, Amit Z (1999) Exposure to nicotine enhances acquisition of ethanol drinking by laboratory rats in a limited access paradigm. Psychopharmacology 142:408–412CrossRefPubMedGoogle Scholar
  68. Smith SG, Werner TE, Davis WM (1977) Alcohol-associated conditioned reinforcement. Psychopharmacology 53:223–226CrossRefPubMedGoogle Scholar
  69. Sparks LM, Sciascia JM, Ayorech Z, Chaudhri N (2014) Vendor differences in alcohol consumption and the contribution of dopamine receptors to Pavlovian-conditioned alcohol-seeking in Long-Evans rats. Psychopharmacology 231:753–764CrossRefPubMedGoogle Scholar
  70. Steensland P, Simms JA, Holgate J, Richards JK, Bartlett SE (2007) Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking. Proc Natl Acad Sci U S A 104:12518–12523CrossRefPubMedPubMedCentralGoogle Scholar
  71. Struthers AM, Wilkinson JL, Dwoskin LP, Crooks PA, Bevins RA (2009) Mecamylamine, dihydro-beta-erythroidine, and dextromethorphan block conditioned responding evoked by the conditional stimulus effects of nicotine. Pharmacol Biochem Behav 94:319–328CrossRefPubMedPubMedCentralGoogle Scholar
  72. Vallejo YF, Buisson B, Bertrand D, Green WN (2005) Chronic nicotine exposure upregulates nicotinic receptors by a novel mechanism. J Neurosci 25:5563–5572CrossRefPubMedPubMedCentralGoogle Scholar
  73. Wilson AW, Costall B, Neill JC (2000) Manipulation of operant responding for an ethanol-paired conditioned stimulus in the rat by pharmacological alteration of the serotonergic system. J Psychopharmacol 14:340–346CrossRefPubMedGoogle Scholar
  74. Wise RA (1973) Voluntary ethanol intake in rats following exposure to ethanol on various schedules. Psychopharmacologia 29:203–210CrossRefPubMedGoogle Scholar
  75. Zarrindast MR, Meshkani J, Rezayof A, Beigzadeh R, Rostami P (2010) Nicotinic acetylcholine receptors of the dorsal hippocampus and the basolateral amygdala are involved in ethanol-induced conditioned place preference. Neuroscience 168:505–513CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Psychology, Center for Studies in Behavioral Neurobiology/FRQS Groupe de recherche en neurobiologie comportementaleConcordia UniversityMontrealCanada

Personalised recommendations