, Volume 223, Issue 4, pp 477–487 | Cite as

The effect of morphine dependence on impulsive choice in rats

  • Colin Harvey-Lewis
  • Johnna Perdrizet
  • Keith B. J. FranklinEmail author
Original Investigation



In the human opiate-dependent population, the most consistently reported deficit in executive functioning is impulsivity. Previous research has shown that acute and chronic exposure to drugs of abuse can increase impulsive choice; however, the extent to which opiate dependence contributes to increased impulsivity has not been examined. We report here the effects of morphine dependence on rats’ delay discounting (DD) of a sucrose reward.


We assigned rats randomly to either a dependent group that received a nightly 30 mg/kg subcutaneous dose of morphine or a morphine-naive group that received a nightly saline injection. DD of a sucrose reward was examined in rats prior to initiation of the dosing regimen, 22.5 h after the daily maintenance dose, and after a 14-day abstinence period.


The groups did not differ at baseline, but rats showed accelerated DD while dependent on morphine. After withdrawal from morphine, DD in previously dependent rats was not significantly different from that of naive rats. Since dependent rats also showed reduced motivation to acquire the sucrose reinforcer, we performed a separate experiment to test whether such a decrease in motivation could cause an increase in impulsivity. We found that food-deprived rats switched to a free-feeding diet did not differ in DD from rats maintained at 85 % of free-feeding weight.


An increase in impulsivity can result from physical dependence on morphine and cannot be attributed to changes in motivation to acquire sucrose-reinforced responses.


Delay discounting Morphine dependence Impulsive choice Impulsivity Opiate withdrawal 



This research was supported by grant RGPIN 6303 from The Natural Sciences and Engineering Research Council of Canada. The authors have no conflict of interest to declare and state that the experiments were carried out in conformity with Canadian law.


  1. Anker JJ, Perry JL, Gliddon LA, Carroll ME (2009) Impulsivity predicts the escalation of cocaine self-administration in rats. Pharmacol Biochem Behav 93:343–348PubMedCrossRefGoogle Scholar
  2. Bezzina G, Body S, Cheung THC (2008) Effect of disconnecting the orbital prefrontal cortex from the nucleus accumbens core on inter-temporal choice behaviour: a quantitative analysis. Behav Brain Res 191:272–279PubMedCrossRefGoogle Scholar
  3. Bhargava HN, Villar VM (1992) Pharmacodynamics and pharmacokinetics of intravenously administered morphine in spontaneously hypertensive and normotensive Wistar-Kyoto rats. J Pharmacol Exp Ther 261:290–296PubMedGoogle Scholar
  4. Bickel WK, Marsch LA (2001) Toward a behavioral economic understanding of drug dependence: delay discounting processes. Addiction 96:73–86PubMedCrossRefGoogle Scholar
  5. Bradshaw CM, Szabadi E (1992) Choice between delayed reinforcers in a discrete-trials schedule: the effect of deprivation level. Q J Exp Psychol B 44:1–6PubMedGoogle Scholar
  6. Cooper ZD, Truong YNT, Shi YG, Woods JH (2008) Morphine deprivation increases self-administration of the fast- and short-acting mu-opioid receptor agonist remifentanil in the rat. J Pharmacol Exp Ther 326:920–929PubMedCrossRefGoogle Scholar
  7. Crews FT, Boettiger CA (2009) Impulsivity, frontal lobes and risk for addiction. Pharmacol Biochem Behav 93:237–247PubMedCrossRefGoogle Scholar
  8. Dallery J, Locey ML (2005) Effects of acute and chronic nicotine on impulsive choice in rats. Behav Pharmacol 16:15–23PubMedCrossRefGoogle Scholar
  9. de Wit H (2009) Impulsivity as a determinant and consequence of drug use: a review of underlying processes. Addict Biol 14:22–31PubMedCrossRefGoogle Scholar
  10. Eisenberger R, Masterson FA, Lowman K (1982) Effects of previous delay of reward, generalized effort, and deprivation on impulsiveness. Learn Motiv 13:378–389CrossRefGoogle Scholar
  11. Ekblom M, Hammarlund-Udenaes M, Paalzow L (1993) Modeling of tolerance development and rebound effect during different intravenous administrations of morphine to rats. J Pharmacol Exp Ther 266:244–252PubMedGoogle Scholar
  12. Franklin KBJ, Abbott F (1989) Techniques for assessing the effects of drugs on nociceptive responses. Neuromethods 13:145Google Scholar
  13. George O, Koob GF (2010) Individual differences in prefrontal cortex function and the transition from drug use to drug dependence. Neurosci Biobehav Rev 35:232–247PubMedCrossRefGoogle Scholar
  14. Giordano LA, Bickel WK, Loewenstein G, Jacobs EA, Marsch L, Badger GJ (2002) Mild opioid deprivation increases the degree that opioid-dependent outpatients discount delayed heroin and money. Psychopharmacology 163:174–182PubMedCrossRefGoogle Scholar
  15. Grimm JW, Hope BT, Wise RA, Shaham Y (2001) Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature 412:141–142PubMedCrossRefGoogle Scholar
  16. Hand TH, Franklin KBJ (1986) Associative factors in the effects of morphine on self-stimulation. Psychopharmacology 88:472–479PubMedCrossRefGoogle Scholar
  17. Harty SC, Whaley JE, Halperin JM, Ranaldi R (2011) Impulsive choice, as measured in a delay discounting paradigm, remains stable after chronic heroin administration. Pharmacol Biochem Behav 98:337–340PubMedCrossRefGoogle Scholar
  18. Herrnstein RJ (1970) On the law of effect. J Exp Anal Behav 13:243–266PubMedCrossRefGoogle Scholar
  19. Ho MY, Mobini S, Chiang TJ, Bradshaw CM, Szabadi E (1999) Theory and method in the quantitative analysis of “impulsive choice” behaviour: implications for psychopharmacology. Psychopharmacology 146:362–372PubMedCrossRefGoogle Scholar
  20. Jacobs EH, Smit AB, de Vries TJ, Schoffelmeer ANM (2003) Neuroadaptive effects of active versus passive drug administration in addiction research. Trends Pharmacol Sci 24:566–573PubMedCrossRefGoogle Scholar
  21. Kieres AK, Hausknecht KA, Farrar AM, Acheson A, de Wit H, Richards JB (2004) Effects of morphine and naltrexone on impulsive decision making in rats. Psychopharmacology (Berl) 173:167–174CrossRefGoogle Scholar
  22. Kirby KN, Petry NM (2004) Heroin and cocaine abusers have higher discount rates for delayed rewards than alcoholics or non-drug-using controls. Addiction 99:461–471PubMedCrossRefGoogle Scholar
  23. Kirby KN, Petry NM, Bickel WK (1999) Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls. J Exp Psychol Gen 128:78–87PubMedCrossRefGoogle Scholar
  24. Lenoir M, Ahmed SH (2007) Heroin-induced reinstatement is specific to compulsive heroin use and dissociable from heroin reward and sensitization. Neuropsychopharmacology 32:616–624PubMedCrossRefGoogle Scholar
  25. Madden GJ, Petry NM, Badger GJ, Bickel WK (1997) Impulsive and self-control choices in opioid-dependent patients and non-drug-using control patients: Drug and monetary rewards. Exp Clin Psychol 5:256–262CrossRefGoogle Scholar
  26. Mar AC, Robbins TW (2007) Delay discounting and impulsive choice in the rat. Curr Protoc Neurosci Chapter 8: Unit 8.22.Google Scholar
  27. Mar AC, Walker ALJ, Theobald DE, Eagle DM, Robbins TW (2011) Dissociable effects of lesions to orbitofrontal cortex subregions on impulsive choice in the rat. J Neurosci 31:6398–6404PubMedCrossRefGoogle Scholar
  28. Mendez IA, Simon NW, Hart N, Mitchell MR, Nation JR, Wellman PJ, Setlow B (2010) Self-administered cocaine causes long-lasting increases in impulsive choice in a delay discounting task. Behav Neurosci 124:470–477PubMedCrossRefGoogle Scholar
  29. Myerson J, Green L, Warusawitharana M (2001) Area under the curve as a measure of discounting. J Exp Anal Behav 76:235–243PubMedCrossRefGoogle Scholar
  30. Paine TA, Dringenberg HC, Olmstead MC (2003) Effects of chronic cocaine on impulsivity: relation to cortical serotonin mechanisms. Behav Brain Res 147:135–147PubMedCrossRefGoogle Scholar
  31. Pau CW, Lee TM, Chan SF (2002) The impact of heroin on frontal executive functions. Arch Clin Neuropsychol 17:663–670PubMedGoogle Scholar
  32. Perry JL, Carroll ME (2008) The role of impulsive behavior in drug abuse. Psychopharmacology (Berl) 200:1–26CrossRefGoogle Scholar
  33. Poulos CX, Le AD, Parker JL (1995) Impulsivity predicts individual susceptibility to high levels of alcohol self-administration. Behav Pharmacol 6:810–814PubMedCrossRefGoogle Scholar
  34. Richards JB, Sabol KE, de Wit H (1999) Effects of methamphetamine on the adjusting amount procedure, a model of impulsive behavior in rats. Psychopharmacology 146:432–439PubMedCrossRefGoogle Scholar
  35. Setlow B, Mendez IA, Mitchell MR, Simon NW (2009) Effects of chronic administration of drugs of abuse on impulsive choice (delay discounting) in animal models. Behav Pharmacol 20:380–389PubMedCrossRefGoogle Scholar
  36. Simon NW, Mendez IA, Setlow B (2007) Cocaine exposure causes long-term increases in impulsive choice. Behav Neurosci 121:543–549PubMedCrossRefGoogle Scholar
  37. South SM, Edwards SR, Smith MT (2009) Antinociception versus serum concentration relationships following acute administration of intravenous morphine in male and female Sprague–Dawley rats: differences between the tail flick and hot plate nociceptive tests. Clin Exp Pharmacol Physiol 36:20–28PubMedCrossRefGoogle Scholar
  38. Stain F, Barjavel MJ, Sandouk P, Plotkine M, Scherrmann JM, Bhargava HN (1995) Analgesic response and plasma and brain extracellular fluid pharmacokinetics of morphine and morphine-6-beta-d-glucuronide in the rat. J Pharmacol Exp Ther 274:852–857PubMedGoogle Scholar
  39. Stewart J, de Wit H, Eikelboom R (1984) Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol Rev 91:251–268PubMedCrossRefGoogle Scholar
  40. Strandberg JJ, Kugelberg FC, Alkass K, Gustavsson A, Zahlsen K, Spigset O, Druid H (2006) Toxicological analysis in rats subjected to heroin and morphine overdose. Toxicol Lett 166:11–18PubMedCrossRefGoogle Scholar
  41. Tjon GH, De Vries TJ, Nestby P, Wardeh G, Mulder AH, Schoffelmeer AN (1995) Intermittent and chronic morphine treatment induces long-lasting changes in delta-opioid receptor-regulated acetylcholine release in rat striatum and nucleus accumbens. Eur J Pharmacol 283:169–176PubMedCrossRefGoogle Scholar
  42. Winstanley CA, LaPlant Q, Theobald DE, Green TA, Bachtell RK, Perrotti LI, DiLeone RJ, Russo SJ, Garth WJ, Self DW, Nestler EJ (2007) DeltaFosB induction in orbitofrontal cortex mediates tolerance to cocaine-induced cognitive dysfunction. J Neurosci 27:10497–10507PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Colin Harvey-Lewis
    • 1
  • Johnna Perdrizet
    • 1
  • Keith B. J. Franklin
    • 1
    Email author
  1. 1.Department of PsychologyMcGill UniversityMontrealCanada

Personalised recommendations