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Psychopharmacology

, Volume 236, Issue 9, pp 2835–2846 | Cite as

Conditioned stimuli affect ethanol-seeking by female alcohol-preferring (P) rats: the role of repeated-deprivations, cue-pretreatment, and cue-temporal intervals

  • Sheketha R. HauserEmail author
  • Gerald A. DeehanJr
  • Christopher P. Knight
  • Robert A. Waeiss
  • William A. Truitt
  • Philip L. Johnson
  • Richard L. Bell
  • William J. McBride
  • Zachary A. Rodd
Original Investigation

Abstract

Rationale

Evidence indicates that drug-paired stimuli can evoke drug-craving leading to drug-seeking and repeated relapse periods can influence drug-seeking behaviors.

Objectives

The present study examined (1) the effect of an interaction between repeated deprivation cycles and excitatory conditioning stimuli (CS+) on ethanol (EtOH)-seeking; (2) the effects of EtOH-paired cue-exposure in a non-drug-paired environment on subsequent conditioning in a drug-paired environment; and (3) the temporal effects of conditioned cues on subsequent EtOH-seeking.

Methods

Adult female alcohol-preferring (P) rats were exposed to three conditioned odor cues; CS+ associated with EtOH self-administration, CS− associated with the absence of EtOH (extinction training), and a neutral stimulus (CS0) presented in a neutral non-drug-paired environment. The rats underwent four deprivation cycles or were non-deprived, following extinction they were maintained in a home cage for an EtOH-free period, and then exposed to no cue, CS+, CS−, or CS0 to assess the effect of the conditioned cues on EtOH-seeking behavior.

Results

Repeated deprivations enhanced and prolonged the duration of CS+ effects on EtOH-seeking. Presentation of the CS− in a non-drug-paired environment blocked the ability of a CS+ to enhance EtOH-seeking in a drug-paired environment. Presentation of the CS+ or CS− in a non-drug-paired environment 2 or 4 h earlier significantly altered EtOH-seeking.

Conclusion

Results indicated an interaction between repeated deprivation cycles and CS+ resulted in a potentiation of CS+ evoked EtOH-seeking. In addition, a CS− may have therapeutic potential by providing prophylactic protection against relapse behavior in the presence of cues in the drug-using environment.

Keywords

Drug-seeking Drug-craving Drug relapse Drug deprivation Alcohol relapse Alcohol-preferring (P) rats 

Notes

Funding

The work was supported in part by NIAAA grants AA07611, AA07462, AA020908, AA022287, and AA024612.

Compliance with ethical standards

All research protocols were approved by the institutional animal care and use committee and are in accordance with the guidelines of the Institutional Care and Use Committee of the National Institute on Drug Abuse, National Institutes of Health, and the Guide for the Care and Use of Laboratory Animals.

Conflict of interest

The authors declare that they have no conflict of interest.

Disclosures

The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIAAA or NIH.

References

  1. Bell RL, Sable HJ, Colombo G, Hyytia P, Rodd ZA, Lumeng L (2012) Animal models for medications development targeting alcohol abuse using selectively bred rat lines: neurobiological and pharmacological validity. Pharmacol Biochem Behav 103:119–155CrossRefGoogle Scholar
  2. Bell RL, Hauser S, Rodd ZA, Liang T, Sari Y, McClintick J, Rahman S, Engleman EA (2016) A genetic animal model of alcoholism for screening medications to treat addiction. Int Rev Neurobiol 126:179–261CrossRefGoogle Scholar
  3. Bell RL, Hauser SR, Liang T, Sari Y, Maldonado-Devincci A, Rodd ZA (2017) Rat animal models for screening medications to treat alcohol use disorders. Neuropharmacology 122:201–243CrossRefGoogle Scholar
  4. Bouton ME (2004) Context and behavioral processes in extinction. Learn Mem 11:485–494CrossRefGoogle Scholar
  5. Bouton ME, Todd TP, Vurbic D, Winterbauer NE (2011) Renewal after the extinction of free operant behavior. Learn Behav 39:57–67CrossRefGoogle Scholar
  6. Brooks DC (2000) Recent and remote extinction cues reduce spontaneous recovery. Q J Exp Psychol B 53:25–58CrossRefGoogle Scholar
  7. Brooks DC, Bouton ME (1993) A retrieval cue for extinction attenuates spontaneous recovery. J Exp Psychol Anim Behav Process 19:77–89CrossRefGoogle Scholar
  8. Brown ME, Anton RF, Malcolm R, Ballenger JC (1988) Alcohol detoxification and withdrawal seizures: clinical support for a kindling hypothesis. Biol Psychiatry 23:507–514CrossRefGoogle Scholar
  9. Burish TG, Maisto SA, Cooper AM, Sobell MB (1981) Effects of voluntary short-term abstinence from alcohol on subsequent drinking patterns of college students. J Stud Alcohol 42:1013–1020CrossRefGoogle Scholar
  10. Chaudhri N, Woods CA, Sahuque LL, Gill TM, Janak PH (2013) Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of Pavlovian-conditioned alcohol-seeking. Eur J Neurosci 38:2751–2761CrossRefGoogle Scholar
  11. Ciccocioppo R, Angeletti S, Weiss F (2001) Long-lasting resistance to extinction of response reinstatement induced by ethanol-related stimuli: role of genetic ethanol preference. Alcohol Clin Exp Res 25:1414–1419CrossRefGoogle Scholar
  12. Ciccocioppo R, Martin-Fardon R, Weiss F (2002) Effect of selective blockade of mu(1) or delta opioid receptors on reinstatement of alcohol-seeking behavior by drug-associated stimuli in rats. Neuropsychopharmacology 27:391–399CrossRefGoogle Scholar
  13. Ciccocioppo R, Lin D, Martin-Fardon R, Weiss F (2003) Reinstatement of ethanol-seeking behavior by drug cues following single versus multiple ethanol intoxication in the rat: effects of naltrexone. Psychopharmacology 168:208–215CrossRefGoogle Scholar
  14. Conklin CA, Robin N, Perkins KA, Salkeld RP, McClernon FJ (2008) Proximal versus distal cues to smoke: the effects of environments on smokers’ cue-reactivity. Exp Clin Psychopharmacol 16:207–214CrossRefGoogle Scholar
  15. Conklin CA, Perkins KA, Robin N, McClernon FJ, Salkeld RP (2009) Bringing the real world into the laboratory: personal smoking and non-smoking environments. Drug Alcohol Depend 111:58–63CrossRefGoogle Scholar
  16. Drummond DC (2000) What does cue-reactivity have to offer clinical research? Addiction 95(Suppl 2):S129–S144CrossRefGoogle Scholar
  17. Duka T, Gentry J, Malcolm R, Ripley TL, Borlikova G, Stephens DN, Veatch LM, Becker HC, Crews FT (2004) Consequences of multiple withdrawals from alcohol. Alcohol Clin Exp Res 28:233–246CrossRefGoogle Scholar
  18. Fatseas M, Serre F, Alexandre JM, Debrabant R, Auriacombe M, Swendsen J (2015) Craving and substance use among patients with alcohol, tobacco, cannabis or heroin addiction: a comparison of substance- and person-specific cues. Addiction 110:1035–1042CrossRefGoogle Scholar
  19. Ferri M, Amato L, Davoli M (2006) Alcoholics Anonymous and other 12-step programmes for alcohol dependence. Cochrane Database Syst Rev (3):CD005032Google Scholar
  20. Fuchs RA, Lasseter HC, Ramirez DR, Xie X (2008) Relapse to drug seeking following prolonged abstinence: the role of environmental stimuli. Drug Discov Today Dis Models 5:251–258CrossRefGoogle Scholar
  21. Hauser SR, Ding ZM, Getachew B, Toalston JE, Oster SM, McBride WJ, Rodd ZA (2011) The posterior ventral tegmental area mediates alcohol-seeking behavior in alcohol-preferring rats. J Pharmacol Exp Ther 336:857–865CrossRefGoogle Scholar
  22. Hauser SR, Deehan GA Jr, Knight CP, Toalston JE, McBride WJ, Rodd ZA (2016) Parameters of context-induced ethanol (EtOH)-seeking in alcohol-preferring (P) rats: temporal analysis, effects of repeated deprivation, and EtOH priming injections. Alcohol Clin Exp Res 40:2229–2239CrossRefGoogle Scholar
  23. Hilbrom ME (1990) Alcohol withdrawal seizures and binge versus chronic drinking. In: Port RJ, Mattson RH, Cramer JA, Diamond I (eds) Alcohol and seizures: basic mechanisms and clinical concepts. FA Davis, Philadelphia, pp 206–215Google Scholar
  24. Honig WK, Staddon JER (1977) Handbook of operant behavior. Prentice-Hall, Englewood CliffsGoogle Scholar
  25. Janak PH, Chaudhri N (2010) The potent effect of environmental context on relapse to alcohol-seeking after extinction. Open Addict J 3:76–87CrossRefGoogle Scholar
  26. Kearns DN, Weiss SJ, Schindler CW, Panlilio LV (2005) Conditioned inhibition of cocaine seeking in rats. J Exp Psychol Anim Behav Process 31:247–253CrossRefGoogle Scholar
  27. Knight CP, Hauser SR, Deehan GA Jr, Toalston JE, McBride WJ, Rodd ZA (2016) Oral conditioned cues can enhance or inhibit ethanol (EtOH)-seeking and EtOH relapse drinking by alcohol-preferring (P) rats. Alcohol Clin Exp Res 40:906–915CrossRefGoogle Scholar
  28. Le Moal M, Koob GF (2007) Drug addiction: pathways to the disease and pathophysiological perspectives. Eur Neuropsychopharmacol 17:377–393CrossRefGoogle Scholar
  29. Liu X, Weiss F (2002) Reversal of ethanol-seeking behavior by D1 and D2 antagonists in an animal model of relapse: differences in antagonist potency in previously ethanol-dependent versus nondependent rats. J Pharmacol Exp Ther 300:882–889CrossRefGoogle Scholar
  30. Malcolm R, Herron JE, Anton RF, Roberts J, Moore J (2000a) Recurrent detoxification may elevate alcohol craving as measured by the Obsessive Compulsive Drinking Scale. Alcohol 20:181–185CrossRefGoogle Scholar
  31. Malcolm R, Roberts JS, Wang W, Myrick H, Anton RF (2000b) Multiple previous detoxifications are associated with less responsive treatment and heavier drinking during an index outpatient detoxification. Alcohol 22:159–164CrossRefGoogle Scholar
  32. McClernon FJ, Conklin CA, Kozink RV, Adcock RA, Sweitzer MM, Addicott MA, Chou YH, Chen NK, Hallyburton MB, DeVito AM (2016) Hippocampal and insular response to smoking-related environments: neuroimaging evidence for drug-context effects in nicotine dependence. Neuropsychopharmacology 41:877–885CrossRefGoogle Scholar
  33. McKinzie DL, Nowak KL, Yorger L, McBride WJ, Murphy JM, Lumeng L, Li TK (1998) The alcohol deprivation effect in the alcohol-preferring P rat under free-drinking and operant access conditions. Alcohol Clin Exp Res 22:1170–1176CrossRefGoogle Scholar
  34. McMillen BA (1997) Toward a definition of a valid animal model of alcoholism: multiple animal models for multiple diseases. Alcohol 14:409–419CrossRefGoogle Scholar
  35. McNally GP (2014) Extinction of drug seeking: neural circuits and approaches to augmentation. Neuropharmacology 76(Pt B):528–532CrossRefGoogle Scholar
  36. Millan EZ, Kim HA, Janak PH (2017) Optogenetic activation of amygdala projections to nucleus accumbens can arrest conditioned and unconditioned alcohol consummatory behavior. Neuroscience 360:106–111CrossRefGoogle Scholar
  37. O’Brien CP, Childress AR, McLellan T, Ehrman R (1998) Integrating systemic cue exposure with standard treatment in recovering drug dependent patients. Addict Behav 15:355–365CrossRefGoogle Scholar
  38. O'Brien CP, Alterman A, Childress AR, McLellan AT (1992) Developing and evaluating new treatments for alcoholism and cocaine dependence. Recent Dev Alcohol 10:303–325CrossRefGoogle Scholar
  39. Oster SM, Toalston JE, Kuc KA, Pommer TJ, Murphy JM, Lumeng L, Bell RL, McBride WJ, Rodd ZA (2006) Effects of multiple alcohol deprivations on operant ethanol self-administration by high-alcohol-drinking replicate rat lines. Alcohol 38:155–164CrossRefGoogle Scholar
  40. Research Institute for Laboratory Animal Research (2011) Guide for the care and use of laboratory animals, 8th edn. The National Academies Press, Washington, D.CGoogle Scholar
  41. Rodd ZA, Bell RL, Kuc KA, Murphy JM, Lumeng L, Li T-K, McBride WJ (2003) Effects of repeated alcohol deprivations on operant ethanol self-administration by alcohol-preferring (P) rats. Neuropsychopharmacology 28:1614–1621CrossRefGoogle Scholar
  42. Rodd ZA, Bell RL, Sable HJ, Murphy JM, McBride WJ (2004) Recent advances in animal models of alcohol craving and relapse. Pharmacol Biochem Behav 79:439–450CrossRefGoogle Scholar
  43. Rodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li T-K, Lumeng L, McBride WJ (2005a) Prolonged increase in the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol following repeated exposure to cycles of ethanol access and deprivation. J Pharmacol Exp Ther 315:648–657CrossRefGoogle Scholar
  44. Rodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li TK, Lumeng L, McBride WJ (2005b) Chronic ethanol drinking by alcohol-preferring rats increases the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol. Alcohol Clin Exp Res 29:358–366CrossRefGoogle Scholar
  45. Rodd ZA, McKinzie DL, Bell RL, McQueen VK, Murphy JM, Schoepp DD, McBride WJ (2006) The metabotropic glutamate 2/3 receptor agonist LY404039 reduces alcohol-seeking but not alcohol self-administration in alcohol-preferring (P) rats. Behav Brain Res 171:207–215CrossRefGoogle Scholar
  46. Rodd-Henricks ZA, Bell RL, Kuc KA, Murphy JM, McBride WJ, Lumeng L, Li T-K (2002a) Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: I. Periadolescent exposure. Alcohol Clin Exp Res 26:1632–1641CrossRefGoogle Scholar
  47. Rodd-Henricks ZA, Bell RL, Kuc KA, Murphy JM, McBride WJ, Lumeng L, Li T-K (2002b) Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: II. Adult exposure. Alcohol Clin Exp Res 26:1642–1652CrossRefGoogle Scholar
  48. Rosenthal MZ, Kutlu MG (2014) Translation of associative learning models into extinction reminders delivered via mobile phones during cue exposure interventions for substance use. Psychol Addict Behav 28:863–871CrossRefGoogle Scholar
  49. Sciascia JM, Mendoza J, Chaudhri N (2014) Blocking dopamine d1-like receptors attenuates context-induced renewal of pavlovian-conditioned alcohol-seeking in rats. Alcohol Clin Exp Res 38:418–427CrossRefGoogle Scholar
  50. Szczytkowski JL, Fuchs RA, Lysle DT (2011) Ventral tegmental area-basolateral amygdala-nucleus accumbens shell neurocircuitry controls the expression of heroin-conditioned immunomodulation. J Neuroimmunol 237:47–56CrossRefGoogle Scholar
  51. Willcocks AL, McNally GP (2014) An extinction retrieval cue attenuates renewal but not reacquisition of alcohol seeking. Behav Neurosci 128:83–91CrossRefGoogle Scholar
  52. Wright TM, Myrick H, Malcolm R, Randall P, Boyle E, Henderson S, Anton R (2007) Impact of lifetime alcohol quit attempts and medicated detoxifications on time to relapse during an index alcohol detoxification. J Addict Med 1:15–20CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sheketha R. Hauser
    • 1
    Email author
  • Gerald A. DeehanJr
    • 2
  • Christopher P. Knight
    • 1
  • Robert A. Waeiss
    • 3
  • William A. Truitt
    • 4
  • Philip L. Johnson
    • 4
  • Richard L. Bell
    • 1
  • William J. McBride
    • 1
  • Zachary A. Rodd
    • 1
  1. 1.Department of PsychiatryIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of PsychologyEast Tennessee State UniversityJohnson CityUSA
  3. 3.Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research InstituteIndianapolisUSA
  4. 4.Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisUSA

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