Psychopharmacology

, Volume 197, Issue 3, pp 409–419

The effects of nicotine on ethanol-induced conditioned taste aversions in Long–Evans rats

  • Jennifer A. Rinker
  • Gregory D. Busse
  • Peter G. Roma
  • Scott A. Chen
  • Christina S. Barr
  • Anthony L. Riley
Original Investigation
  • 122 Downloads

Abstract

Rationale

Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter of which is reportedly affected by polydrug use.

Objectives

Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine’s impact on ethanol’s aversive effects within a conditioned taste aversion design.

Materials and methods

Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment 2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment 3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally, nicotine’s effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined.

Results

Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination.

Conclusions

These data demonstrate that nicotine may interact with ethanol, increasing ethanol’s aversive effects. Although the rewarding effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered nicotine. It is more likely attributable to nicotine-related changes in ethanol’s rewarding effects.

Keywords

Nicotine Ethanol Drug interactions Polydrug use Drug acceptability Conditioned taste aversion Hypothermia Blood alcohol Rats Female 

References

  1. Adir J, Wildfeuer W, Miller RP (1980) Effect of ethanol pretreatment on the pharmacokinetics of nicotine in rats. J Pharmacol Exp Ther 212:274–279PubMedGoogle Scholar
  2. Amit Z, Levitan DE, Brown ZW, Rogan F (1977) Possible involvement of central factors in the mediation of conditioned taste aversion. Neuropharmacology 16:121–124PubMedCrossRefGoogle Scholar
  3. Baker TB, Cannon DS (1982) Alcohol and taste-mediated learning. Addict Behav 7:211–230PubMedCrossRefGoogle Scholar
  4. Barker LM, Johns T (1978) Effect of ethanol preexposure on ethanol-induced conditioned taste aversion. J Stud Alcohol 39:39–46PubMedGoogle Scholar
  5. Barrett SP, Tichauer M, Leyton M, Pihl RO (2006) Nicotine increases alcohol self-administration in non-dependent male smokers. Drug Alcohol Depend 81:197–204PubMedCrossRefGoogle Scholar
  6. Batel P, Pessione F, Maitre C, Rueff B (1995) Relationship between alcohol and tobacco dependencies among alcoholics who smoke. Addiction 90:977–980PubMedCrossRefGoogle Scholar
  7. Bienkowski P, Kuca P, Piasecki J, Kostowski W (1996) Low dose of ethanol induces conditioned place preference in rats after repeated exposures to ethanol or saline injections. Alcohol Alcohol 31:547–553PubMedGoogle Scholar
  8. Bienkowski P, Piasecki J, Koros E, Stefanski R, Kostowski W (1998) Studies on the role of nicotinic acetylcholine receptors in the discriminative and aversive stimulus properties of ethanol in the rat. Eur Neuropsychopharmacol 8:79–87PubMedCrossRefGoogle Scholar
  9. Braveman NS (1975) Formation of taste aversions in rats following prior exposure to sickness. Learn Motiv 6:512–534CrossRefGoogle Scholar
  10. Broadbent J, Muccino KJ, Cunningham CL (2002) Ethanol-induced conditioned taste aversion in 15 inbred mouse strains. Behav Neurosci 116:138–148PubMedCrossRefGoogle Scholar
  11. Brown ZW, Amit Z, Smith B, Rockman GE (1978) Differential effects on conditioned taste aversion learning with peripherally and centrally administered acetaldehyde. Neuropharmacology 17:931–935PubMedCrossRefGoogle Scholar
  12. Cailhol S, Mormede P (2002) Conditioned taste aversion and alcohol drinking: strain and gender differences. J Stud Alcohol 63:91–99PubMedGoogle Scholar
  13. Chester JA, Risinger FO, Cunningham CL (1998) Ethanol reward and aversion in mice bred for sensitivity to ethanol withdrawal. Alcohol Clin Exp Res 22:468–473PubMedGoogle Scholar
  14. Clark A, Lindgren S, Brooks SP, Watson WP, Little HJ (2001) Chronic infusion of nicotine can increase operant self-administration of alcohol. Neuropharmacology 41:108–117PubMedCrossRefGoogle Scholar
  15. Cunningham CL, Hawks DM, Niehus DR (1988) Role of hypothermia in ethanol-induced conditioned taste aversion. Psychopharmacology (Berl) 95:318–322CrossRefGoogle Scholar
  16. Cunningham CL, Niehus JS, Bachtold JF (1992) Ambient temperature effects on taste aversion conditioned by ethanol: contribution of ethanol-induced hypothermia. Alcohol Clin Exp Res 16:1117–1124PubMedCrossRefGoogle Scholar
  17. Elkins RL, Orr TE, Li JQ, Walters PA, Whitford JL, Carl GF, Rausch JL (2000) Serotonin reuptake is less efficient in taste aversion resistant than in taste aversion-prone rats. Pharmacol Biochem Behav 66:609–614PubMedCrossRefGoogle Scholar
  18. Elkins RL, Orr TE, Edwards GL, Storming TA, Fei Y, Carl GF, Hobbs SH, Buccafusco JJ, Rausch JL (2003) Cocaine-induced expression differences of 5-HT3 receptors and Na+/K+-APTase pump subunits in amygdalae of taste-aversion-prone and taste-aversion-resistant rats. Ann N Y Acad Sci 985:519–521CrossRefGoogle Scholar
  19. Escarabajal MD, De Witte P, Quertemont E (2003) Role of acetaldehyde in ethanol-induced conditioned taste aversion in rats. Psychopharmacology (Berl) 167:130–136Google Scholar
  20. Etkind SA, Fantegrossi WE, Riley AL (1998) Cocaine and alcohol synergism in taste aversion learning. Pharmacol Biochem Behav 59:649–655PubMedCrossRefGoogle Scholar
  21. Etscorn F, Moore GA, Hagen LS, Caton TM, Sanders DL (1986) Saccharin aversions in hamsters as a result of nicotine injections. Pharmacol Biochem Behav 24:567–570PubMedCrossRefGoogle Scholar
  22. Etscorn F, Moore GA, Scott EP, Hagen LS, Caton TM, Sanders DL, Divine KK (1987) Conditioned saccharin aversions in rats as a result of cutaneous nicotine or intraperitoneal nicotine administered in divided doses. Pharmacol Biochem Behav 28:495–502PubMedCrossRefGoogle Scholar
  23. Freeman KB, Riley AL (2008) The origins of conditioned taste aversion learning: an historical analysis. In: Reilly S, Schachtman TD (eds) Conditioned taste aversion: behavioral and neural processes. Oxford University Press, New York, NY (in press) Google Scholar
  24. Garcia J, Ervin FR (1968) Appetites, aversions, and addictions: a model for visceral memory. Recent Adv Biol Psychiatry 10:284–293PubMedGoogle Scholar
  25. Garcia J, Kimeldorf DJ, Koelling RA (1955) Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science 122:157–158PubMedCrossRefGoogle Scholar
  26. Grabus SD, Martin BR, Brown SE, Damaj MI (2006) Nicotine place preference in the mouse: influences of prior handling, dose and strain and attenuation by nicotinic receptor antagonists. Psychopharmacology (Berl) 184:456–463CrossRefGoogle Scholar
  27. Grakalic I, Riley AL (2002) Asymmetric serial interactions between ethanol and cocaine in taste aversion learning. Pharmacol Biochem Behav 73:787–795PubMedCrossRefGoogle Scholar
  28. Grigson PS (1997) Conditioned taste aversions and drugs of abuse: a reinterpretation. Behav Neurosci 111:129–136PubMedCrossRefGoogle Scholar
  29. Hisaoka M, Levy G (1985) Kinetics of drug action in disease states XI: effect of nicotine on the pharmacodynamics and pharmacokinetics of phenobarbital and ethanol in rats. J Pharm Sci 74:412–415PubMedCrossRefGoogle Scholar
  30. Hunt T, Amit Z (1987) Conditioned taste aversion induced by self-administered drugs: paradox revisited. Neurosci Biobehav Rev 11:107–130PubMedCrossRefGoogle Scholar
  31. Iwamoto ET, Williamson EC (1984) Nicotine-induced taste aversion: characterization and preexposure effects in rats. Pharmacol Biochem Behav 21:527–532PubMedCrossRefGoogle Scholar
  32. Jones JD, Busse GD, Riley AL (2006) Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions. Pharmacol Biochem Behav 83:554–560PubMedCrossRefGoogle Scholar
  33. Korkosz A, Scinska A, Taracha E, Plaznik A, Kukwa A, Kostowski W, Bienkowski P (2006a) Nicotine-induced conditioned taste aversion in the rat: effects of ethanol. Eur J Pharmacol 537:99–105PubMedCrossRefGoogle Scholar
  34. Korkosz A, Zatorski P, Taracha E, Plaznik A, Kostowski W, Bienkowski P (2006b) Effects of ethanol on nicotine-induced conditioned place preference in C57BL/6J mice. Prog Neuropsychopharmacol Biol Psychiatry 30:1283–1290PubMedCrossRefGoogle Scholar
  35. 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 75:55–65PubMedCrossRefGoogle Scholar
  36. Kozlowski LT, Ferrence RG, Corbit T (1990) Tobacco use: a perspective for alcohol and drug researchers. Br J Addict 85:245PubMedCrossRefGoogle Scholar
  37. Kunin D, Smith BR, Amit Z (1999) Nicotine and ethanol interaction on conditioned taste aversions induced by both drugs. Pharmacol Biochem Behav 62:215–221PubMedCrossRefGoogle Scholar
  38. Kunin D, Bloch RT, Smith BR, Amit Z (2001) Caffeine, nicotine and mecamylamine share stimulus properties in the preexposure conditioned taste aversion procedure. Psychopharmacology (Berl) 159:70–76CrossRefGoogle Scholar
  39. Leonard B (1997) Fundamentals of psychopharmacology, 2nd edn. Wiley, New YorkGoogle Scholar
  40. Lynch WJ, Carroll ME (2001) Regulation of drug intake. Exp Clin Psychopharmacol 9:131–143PubMedCrossRefGoogle Scholar
  41. Mayer LA, Parker LA (1993) Rewarding and aversive properties of IP and SC cocaine: assessment by place and taste conditioning. Psychopharmacology (Berl) 112:189–194CrossRefGoogle Scholar
  42. McClintock MK (1978) Estrous synchrony and its mediation by airborne chemical communication (Rattus norvegicus). Horm Behav 10:264–275PubMedCrossRefGoogle Scholar
  43. Mucha RF (1997) Preferences for tastes paired with a nicotine antagonist in rats chronically treated with nicotine. Pharmacol Biochem Behav 56:175–179PubMedCrossRefGoogle Scholar
  44. National Institute on Alcohol Abuse and Alcoholism (1998) Alcohol Alert No. 39: Alcohol and Tobacco. Available from: http://pubs.niaaa.nih.gov/publications/aa39.htm. Accessed October, 2006
  45. Orr TE, Walters PA, Carl GF, Elkins RL (1993) Brain levels of amines and amino acids in taste aversion-prone and -resistant rats. Physiol Behav 53:495–500PubMedCrossRefGoogle Scholar
  46. 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 30:1408–1413PubMedCrossRefGoogle Scholar
  47. Perkins KA (1997) Combined effects of nicotine and alcohol on subjective, behavioral and physiological responses in humans. Addict Biol 2:255–268CrossRefGoogle Scholar
  48. Perkins KA, Fonte C, Grobe JE (2000) Sex differences in the acute effects of cigarette smoking on the reinforcing value of alcohol. Behav Pharmacol 11:63–70PubMedGoogle Scholar
  49. Pescatore KA, Glowa JR, Riley AL (2005) Strain differences in the acquisition of nicotine-induced conditioned taste aversion. Pharmacol Biochem Behav 82:751–757PubMedCrossRefGoogle Scholar
  50. Quertemont E (2003) Discriminative stimulus effects of ethanol with a conditioned taste aversion procedure: lack of acetaldehyde substitution. Behav Pharmacol 14:343–350PubMedGoogle Scholar
  51. Revusky S, Garcia J (1970) Learned associations over long delays. In: Bower G, Spence J (eds) Psychology of learning and motivation: advances in research and theory. Academic, New York, pp 1–84Google Scholar
  52. Riley AL, Freeman KB (2004) Conditioned flavor aversions: assessment of drug-induced suppression of food intake. In: Crawley JN, Gerfen C, McKay R, Rogawski M, Sibley DR, Skolnick P (eds) Current protocols in neuroscience. Wiley, New York, pp 8.6E.1–8.6E.12Google Scholar
  53. Riley AL, Tuck DL (1985) Conditioned taste aversions: a behavioral index of toxicity. Ann N Y Acad Sci 443:272–292PubMedCrossRefGoogle Scholar
  54. Riley AL, Jacobs WJ, LoLordo VM (1976) Drug exposure and the acquisition and retention of a conditioned taste aversion. J Comp Physiol Psychol 90:799–807PubMedCrossRefGoogle Scholar
  55. Riley AL, Davis CM, Roma PG (2008) Strain differences in taste aversion learning: Implications for animal models of drug abuse. In: Reilly S, Schachtman TR (eds) Conditioned taste aversion: behavioral and neural processes. Oxford University Press, New York (in press)Google Scholar
  56. Risinger FO, Cunningham CL (1998) Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice. Alcohol Clin Exp Res 22:1234–1244PubMedGoogle Scholar
  57. Risinger FO, Oakes RA (1995) Nicotine-induced conditioned place preference and conditioned place aversion in mice. Pharmacol Biochem Behav 51:457–461PubMedCrossRefGoogle Scholar
  58. Risinger FO, Oakes RA (1996) Dose- and conditioning trial-dependent ethanol-induced conditioned place preference in Swiss–Webster mice. Pharmacol Biochem Behav 55:117–123PubMedCrossRefGoogle Scholar
  59. Roma PG, Flint WW, Higley JD, Riley AL (2006) Assessment of the aversive and rewarding effects of alcohol in Fischer and Lewis rats. Psychopharmacology (Berl) 189:187–199CrossRefGoogle Scholar
  60. Romberger DJ, Grant K (2004) Alcohol consumption and smoking status: the role of smoking cessation. Biomed Pharmacother 58:77–83PubMedCrossRefGoogle Scholar
  61. Rose JE, Brauer LH, Behm FM, Cramblett M, Calkins K, Lawhon D (2004) Psychopharmacological interactions between nicotine and ethanol. Nicotine Tob Res 6:133–144PubMedCrossRefGoogle Scholar
  62. Rozin P, Kalat JW (1971) Specific hungers and poison avoidance as adaptive specializations of learning. Psychol Rev 78:459–486PubMedCrossRefGoogle Scholar
  63. Schank JC (2001) Do Norway rats (Rattus norvegicus) synchronize their estrous cycles. Physiol Behav 72:129–139PubMedCrossRefGoogle Scholar
  64. Shoaib M, Stolerman IP, Kumar RC (1994) Nicotine-induced place preferences following prior nicotine exposure in rats. Psychopharmacology (Berl) 113:445–452CrossRefGoogle Scholar
  65. Shoaib M, Zubaran C, Stolerman IP (2000) Antagonism of stimulus properties of nicotine by dihydro-beta-erythroidine (DHbetaE) in rats. Psychopharmacology (Berl) 149:140–146CrossRefGoogle Scholar
  66. Shram MJ, Funk D, Li Z, Le AD (2006) Periadolescent and adult rats respond differently in tests measuring the rewarding and aversive effects of nicotine. Psychopharmacology (Berl) 186:201–208CrossRefGoogle Scholar
  67. Simpson GR, Riley AL (2005) Morphine preexposure facilitates morphine place preference and attenuates morphine taste aversion. Pharmacol Biochem Behav 80:471–479PubMedCrossRefGoogle Scholar
  68. Suzuki T, George FR, Meisch RA (1988) Differential establishment and maintenance of oral ethanol reinforced behavior in Lewis and Fischer 344 inbred rat strains. J Pharmacol Exp Ther 245:164–170PubMedGoogle Scholar
  69. van der Kooy D, O'Shaughnessy M, Mucha RF, Kalant H (1983) Motivational properties of ethanol in naive rats as studied by place conditioning. Pharmacol Biochem Behav 19:441–445PubMedCrossRefGoogle Scholar
  70. White N, Sklar L, Amit Z (1977) The reinforcing action of morphine and its paradoxical side effect. Psychopharmacology (Berl) 52:63–66CrossRefGoogle Scholar
  71. Wise RA, Yokel RA, DeWit H (1976) Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats. Science 191:1273–1275PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jennifer A. Rinker
    • 1
  • Gregory D. Busse
    • 1
  • Peter G. Roma
    • 1
  • Scott A. Chen
    • 2
  • Christina S. Barr
    • 2
  • Anthony L. Riley
    • 1
  1. 1.Psychopharmacology Laboratory, Department of PsychologyAmerican UniversityWashingtonUSA
  2. 2.Laboratory of Clinical and Translational Studies, Section on Primate StudiesNational Institute on Alcohol Abuse and AlcoholismPoolesvilleUSA

Personalised recommendations