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Compulsive drug seeking by rats under punishment: effects of drug taking history

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Abstract

Rationale

Abstinence from drug occurs in human addicts for several reasons, including the avoidance of adverse consequences.

Objectives

To explore a model of drug use in the face of adverse consequences in rats through intermittent punishment of drug seeking and to investigate whether the ability to withhold seeking responses depends upon the duration of drug history.

Materials and methods

Rats were trained under a seeking–taking chained schedule with sucrose or cocaine as reinforcer. Pressing the seeking lever gave access to the taking lever, and a single press on this lever delivered the reinforcer after which the seeking–taking chain recycled. During punishment, half of the seeking links terminated with a mild foot shock without access to the taking link.

Results

After a moderate history of reinforcement, punishment of the terminal response in the seeking link suppressed both sucrose- and cocaine-seeking responses. By contrast, rats with an extended cocaine history were more resistant to punishment than those with a moderate cocaine history. This enhanced resistance to punishment was due to a sub-group of rats that showed minimal or no suppression of drug seeking. No differences in suppression of sucrose seeking were observed in animals with moderate versus extended sucrose histories.

Conclusions

These results suggest that an extended drug self-administration history decreases the ability of vulnerable rats to suppress their drug seeking.

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References

  • American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders. Washington, DC, 4th edn, revised version

    Google Scholar 

  • Burman S (1997) The challenge of sobriety: natural recovery without treatment and self-help groups. J Subst Abuse 9:41–61

    Article  PubMed  CAS  Google Scholar 

  • Caine SB, Lintz R, Koob GF (1992) Intravenous self-administration techniques in animals. In: Sahgal A (ed) Behavioral neuroscience: a practical approach. Oxford Univ. Press, Oxford, pp 117–143

    Google Scholar 

  • Cardinal RN, Robbins TW, Everitt BJ (2000) The effects of d-amphetamine, chlordiazepoxide, alpha-flupenthixol and behavioural manipulations on choice of signalled and unsignalled delayed reinforcement in rats. Psychopharmacology (Berl) 152:362–375

    Article  CAS  Google Scholar 

  • Church RM (1963) The varied effects of punishment on behavior. Psychol Rev 70:369–402

    Article  PubMed  CAS  Google Scholar 

  • Conklin CA, Tiffany ST (2002) Applying extinction research and theory to cue-exposure addiction treatments. Addiction 97(2):155–167

    Article  PubMed  Google Scholar 

  • Corbit LH, Balleine BW (2003) Instrumental and Pavlovian incentive processes have dissociable effects on components of a hetrogeneous instrumental chain. J Exp Psychol Anim Behav Processeses 29:99–106

    Article  Google Scholar 

  • Cunningham JA, Lin E, Ross HE, Walsh GW (2000) Factors associated with untreated remissions from alcohol abuse or dependence. Addict Behav 25:317–321

    Article  PubMed  CAS  Google Scholar 

  • Deroche-Gamonet V, Belin D, Piazza PV (2004) Evidence for addiction-like behavior in the rat. Science 305:1014–1017

    Article  PubMed  CAS  Google Scholar 

  • Dickinson A, Pearce JM (1976) Preference and response suppression under different correlations between shock and a positive reinforcer in rats. Learn Motiv 7:66–85

    Article  Google Scholar 

  • Grove RN, Schuster CR (1974) Suppression of cocaine self-administration by extinction and punishment. Pharmacol Biochem Behav 2:199–208

    Article  PubMed  CAS  Google Scholar 

  • Heyne A, Wolffgramm J (1998) The development of addiction to d-amphetamine in an animal model: same principles as for alcohol and opiate. Psychopharmacology (Berl) 140(4):510–518

    Article  CAS  Google Scholar 

  • Hodos W (1961) Progressive ratio as a measure of reward strength. Science 134:943–944

    Article  PubMed  CAS  Google Scholar 

  • Hutcheson DM, Everitt BJ, Robbins TW, Dickinson A (2001) The role of withdrawal in heroin addiction: enhances reward or promotes avoidance? Nat Neurosci 4:943–947

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, McFarland K (2003) Brain circuitry and the reinstatement of cocaine-seeking behavior. Psychopharmacology (Berl) 168:44–56

    Article  CAS  Google Scholar 

  • Katz JL, Higgins ST (2003) The validity of the reinstatement model of craving and relapse to drug use. Psychopharmacology (Berl) 168(1–2):21–30

    Article  CAS  Google Scholar 

  • Kearns DN, Weiss SJ, Panlilio LV (2002) Conditioned suppression of behavior maintained by cocaine self-administration. Drug Alcohol Depend 65:253–261

    Article  PubMed  CAS  Google Scholar 

  • Klingemann HK (1991) The motivation for change from problem alcohol and heroin use. Br J Addict 86:727–744

    Article  PubMed  CAS  Google Scholar 

  • Lee JL, Everitt BJ, Thomas KL (2004) Independent cellular processes for hippocampal memory consolidation and reconsolidation. Science 304:839–843

    Article  PubMed  CAS  Google Scholar 

  • Miles FJ, Everitt BJ, Dalley JW, Dickinsoon A (2004) Conditioned activity and instrumental reinforcement following long-term oral consumption of cocaine by rats. Behav Neurosci 118:1331–1339

    Article  PubMed  CAS  Google Scholar 

  • Olmstead MC, Parkinson JA, Miles FJ, Everitt BJ, Dickinson A (2000) Cocaine-seeking by rats: regulation, reinforcement and activation. Psychopharmacology (Berl) 152:123–131

    Article  CAS  Google Scholar 

  • Olmstead MC, Lafond MV, Everitt BJ, Dickinson A (2001) Cocaine seeking by rats is a goal-directed action. Behav Neurosci 115:394–402

    Article  PubMed  CAS  Google Scholar 

  • Panlilio LV, Thorndike EB, Schindler CW (2003) Reinstatement of punishment-suppressed opioid self-administration in rats: an alternative model of relapse to drug abuse. Psychopharmacology (Berl) 168:229–235

    Article  CAS  Google Scholar 

  • Schuster CR (1986) Implication of laboratory research for the treatment of drug dependence. In: Goldberg SR, Stolerman IP (eds) Behavioral analysis of drug dependence. Academic, London, pp 375–380

    Google Scholar 

  • Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 168:3–20

    Article  CAS  Google Scholar 

  • Thompson RH, Iwata BA, Conners J, Roscoe EM (1999). Effects of reinforcement for alternative behavior during punishment of self-injury. J Appl Behav Anal 32:317–328

    Article  PubMed  CAS  Google Scholar 

  • Vanderschuren LJ, Everitt BJ (2004) Drug seeking becomes compulsive after prolonged cocaine self-administration. Science 305:1017–1019

    Article  PubMed  CAS  Google Scholar 

  • Waldorf D, Reinarman C, Murphy C (1991) Cocaine changes: the processes of using and quitting cocaine. Temple Univ. Press, Philadelphia

    Google Scholar 

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Acknowledgements

The authors thank M. Aitken for programming and statistical advice, D. Eagle and A. Mar for statistical guidance, K. Hellemans for assistance with the manuscript preparation, J. Lee for general discussion and P. Di Ciano for technical advice.

This research was supported by an MRC Programme Grant No. G9536855 to B. J. Everitt, A. Dickinson and T. W. Robbins and was conducted within the University of Cambridge Behavioural and Clinical Neuroscience Institute, supported by a joint award from the Medical Research Council and the Wellcome Trust.

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Correspondence to Yann Pelloux.

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Appendix 1

A finer analysis of nose poke responding of the whole population during baseline revealed that this response was not evenly distributed throughout the session [F(3,111)=6.2, p = 0.001], but the differences in the pattern of responding varied the group [F(6,111)=2.5, p = 0.025]. Whereas animals with a moderate reinforcer history increased nose poke responding at the end of the session specifically during TO (p < 0.034), the extended sensitive group showed a higher nose poke rate after the first cocaine injection specifically during seeking periods (p < 0.042). However, the pattern of nose poking was differently altered during punishment in the three groups [F(6,111)=3.1, p = 0.008]. Whereas in animals with a moderate reinforcer history, nose poke rate became homogeneous throughout the session, animals with an extended reinforcer history presented a lower nose poke rate at the end of the sessions, specifically during seeking (p < 0.001). In contrary to extended sensitive animals, extended resistant group presented a homogeneous nose poke rate throughout the session both during baseline and punishment (JPEG 49 kb)

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Pelloux, Y., Everitt, B.J. & Dickinson, A. Compulsive drug seeking by rats under punishment: effects of drug taking history. Psychopharmacology 194, 127–137 (2007). https://doi.org/10.1007/s00213-007-0805-0

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  • DOI: https://doi.org/10.1007/s00213-007-0805-0

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