Skip to main content

The effect of acute morphine on delay discounting in dependent and non-dependent rats

Psychopharmacology volume 232, pages 885–895 (2015)Cite this article

Abstract

Rationale

Chronic opiate use is associated with increased impulsivity in both humans and animals, and previous studies suggest that acute morphine can increase impulsivity in non-dependent rats. However, the extent to which chronic opiate usage modulates the effect of acute morphine is unknown.

Methods

Rats were trained to delay discount 20 % sucrose solution and then randomly assigned to either a dependent group that received a nightly 30 mg/kg subcutaneous dose of morphine or a non-dependent group that received a nightly saline injection. Once dependence was established, rats were then assigned to one of four acute morphine doses (0, 1.25, 2.5, 5 mg/kg). For 5 days, delay discounting curves were determined 22.5 h after maintenance doses and 1 h after their prescribed acute injections.

Results

In non-dependent rats, 2.5 and 5 mg/kg doses of morphine caused decreased preference for the large reward at all delays. Acute morphine had no effect on discounting curves in dependent rats.

Conclusions

Morphine dependence can cause tolerance to the effects of acute morphine on delay discounting.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  • Abela AR, Chudasama Y (2013) Dissociable contributions of the ventral hippocampus and orbitofrontal cortex to decision-making with a delayed or uncertain outcome. Eur J Neurosci 37:640–647

    Article  PubMed  Google Scholar 

  • Amato L, Davoli M, Perucci CA, Ferri M (2005) An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. J Subst Abus Treat 28(4), 321–329

  • Andrews JS, Holtzman SG (1988) Effects of d-amphetamine, morphine, naloxone, and drug combinations on visual discrimination in rats. Psychopharmacology 94:172–177

    Article  CAS  PubMed  Google Scholar 

  • Ballard K, Knutson B (2009) Dissociable neural representations of future reward magnitude and delay during temporal discounting. Neuroimage 45:143–150

    Article  PubMed Central  PubMed  Google Scholar 

  • Bartoletti M, Gaiardi M, Gubellini G, Bacchi A, Babbini M (1983) Long-term sensitization to the excitatory effects of morphine. Neuropharmacology 22:1193–1196

    Article  CAS  PubMed  Google Scholar 

  • Bezzina G, Body S, Cheung T (2008) Effect of disconnecting the orbital prefrontal cortex from the nucleus accumbens core on inter-temporal choice behaviour: a quantitative analysis. Behav Brain Res 191:272–279

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bjork JM, Hommer DW, Grant SJ, Danube C (2004) Impulsivity in abstinent alcohol-dependent patients: relation to control subjects and type 1–/type 2–like traits. Alcohol 34:133–150

    Article  PubMed  Google Scholar 

  • Castellano C (1975) Effects of morphine and heroin on discrimination learning and consolidation in mice. Psychopharmacologia 42:235–242

    Article  CAS  PubMed  Google Scholar 

  • Coffey SF, Gudleski GD, Saladin ME, Brady KT (2003) Impulsivity and rapid discounting of delayed hypothetical rewards in cocaine-dependent individuals. Exp Clin Psychopharmacol 11:18–25

    Article  PubMed  Google Scholar 

  • Cooper SJ, Kirkham TC (1990) Basic Mechanisms of Opioids’ Effects on Eating and Drinking. In: Reid LD (ed) Opioids, Bulimia and Alcohol Abuse and Alcoholism. Springer, New York, pp 91–110

    Google Scholar 

  • Dandy KL, Gatch MB (2009) The effects of chronic cocaine exposure on impulsivity in rats. Behav Pharmacol 20:400–405

    Article  CAS  PubMed  Google Scholar 

  • Day JJ, Jones JL, Wightman RM, Carelli RM (2010) Phasic Nucleus Accumbens Dopamine Release Encodes Effort- and Delay-Related Costs. Biol Psychiatry 68:306–309

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • de Wit H, Enggasser JL, Richards JB (2002) Acute administration of d-amphetamine decreases impulsivity in healthy volunteers. Neuropsychopharmacology 27:813–825

    Article  PubMed  Google Scholar 

  • Ferri M, Minozzi S, Bo A, Amato L (2013) Slow-release oral morphine as maintenance therapy for opioid dependence. The Cochrane database of systematic reviews 6: CD009879.

  • Fischer B, Keates A, Bühringer G, Reimer J, Rehm J (2013) Non-medical use of prescription opioids and prescription opioid-related harms: why so markedly higher in North America compared to the rest of the world? Addiction 109:177–181

    Article  PubMed  Google Scholar 

  • Franklin KBJ, Abbott F (1989) Techniques for assessing the effects of drugs on nociceptive responses. Neuromethods 13:145

    Google Scholar 

  • García-Lecumberri C, Torres I, Martín S, Crespo JA, Miguéns M, Nicanor C, Higuera-Matas A, Ambrosio E (2011) Strain differences in the dose-response relationship for morphine self-administration and impulsive choice between Lewis and Fischer 344 rats. J Psychopharmacol 25:783–791

    Article  PubMed  Google Scholar 

  • 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 (Berlin) 163:174–182

    Article  CAS  Google Scholar 

  • Glaser AM, Reyes-Vázquez C, Prieto-Gómez B, Burau K, Dafny N (2012) Morphine administration and abrupt cessation alter the behavioral diurnal activity pattern. Pharmacol Biochem Behav 101:544–552

    Article  CAS  PubMed  Google Scholar 

  • Harvey-Lewis C, Perdrizet J, Franklin KBJ (2012) The effect of morphine dependence on impulsive choice in rats. Psychopharmacology (Berlin) 223:477–487

    Article  CAS  Google Scholar 

  • Heyman GM, Gibb SP (2006) Delay discounting in college cigarette chippers. Behav Pharmacol 17:669–679

    Article  PubMed  Google Scholar 

  • Hoffman WF, Moore M, Templin R, McFarland B, Hitzemann RJ, Mitchell SH (2006) Neuropsychological function and delay discounting in methamphetamine-dependent individuals. Psychopharmacology (Berlin) 188:162–170

    Article  CAS  Google Scholar 

  • Hunt T, Spivak K, Amit Z (1985) Aversive stimulus properties of morphine: evaluation using the drug preexposure conditioned taste aversion paradigm. Behav Neural Biol 44(1):60–73

    Article  CAS  PubMed  Google Scholar 

  • Jo S, Kim K-U, Lee D, Jung MW (2013) Effect of orbitofrontal cortex lesions on temporal discounting in rats. Behav Brain Res 245:22–28

    Article  PubMed Central  PubMed  Google Scholar 

  • Kayir H, Semenova S, Markou A (2014) Baseline impulsive choice predicts the effects of nicotine and nicotine withdrawal on impulsivity in rats. Prog Neuro-Psychopharmacol Biol Psychiatry 48:6–13

    Article  CAS  Google Scholar 

  • Kelsey JE, Niraula A (2013) Effects of acute and sub-chronic nicotine on impulsive choice in rats in a probabilistic delay-discounting task. Psychopharmacologia 227:385–392

    Article  CAS  Google Scholar 

  • 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 (Berlin) 173:167–174

    Article  CAS  Google Scholar 

  • Koek W, Slangen JL (1984) Effects of d-amphetamine and morphine on delayed discrimination: Signal detection analysis and assessment of response repetition in the performance deficits. Psychopharmacology (Berlin) 83:346–350

    Article  CAS  Google Scholar 

  • Kolokotroni KZ, Rodgers RJ, Harrison AA (2013) Trait differences in response to chronic nicotine and nicotine withdrawal in rats. Psychopharmacology (Berlin) 231:567–580

    Article  Google Scholar 

  • LeBlanc AE, Cappell H (1974) Attenuation of punishing effects of morphine and amphetamine by chronic prior treatment. J Comp Physiol 87(4):691–698

    CAS  Google Scholar 

  • 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 Psychopharmacol 5:256–262

    Article  CAS  PubMed  Google Scholar 

  • Mar AC, Walker LJ, Theobald DE, Eagle DM, Robbins TW (2011) Dissociable effects of lesions to orbitofrontal cortex subregions on impulsive choice in the rat. J Neurosci 31:6398–6404

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marshall AT, Smith AP, Kirkpatrick K (2014) Mechanisms of impulsive choice: I. individual differences in interval timing and reward processing. J Exp Anal Behav 102(1):86–101

    Article  PubMed  Google Scholar 

  • Mazur JE (1987) An adjusting procedure for studying delayed reinforcement. In: Commons ML, Mazur JE, Nevin JA, Rachlin H (Eds.), Quantitative analyses of behavior: The effect of delay and of intervening events on reinforcement value, vol. 5. Erlbaum, Hillsdale, NJ, pp. 55–73

  • 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 124:470–477

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ortner CNM (2003) Alcohol intoxication reduces impulsivity in the delay-discounting paradigm. Alcohol Alcohol 38:151–156

    Article  PubMed  Google Scholar 

  • Passetti F, Clark L, Mehta MA, Joyce E, King M (2008) Neuropsychological predictors of clinical outcome in opiate addiction. Drug Alcohol Depend 94:82–91

    Article  CAS  PubMed  Google Scholar 

  • Pattij T, Schetters D, Janssen MC, Wiskerke J, Schoffelmeer AN (2009) Acute effects of morphine on distinct forms of impulsive behavior in rats. Psychopharmacology (Berlin) 205:489–502

    Article  CAS  Google Scholar 

  • Pothuizen HHJ, Jongen-Rêlo AL, Feldon J, Yee BK (2005) Double dissociation of the effects of selective nucleus accumbens core and shell lesions on impulsive-choice behaviour and salience learning in rats. Eur J Neurosci 22:2605–2616

    Article  PubMed  Google Scholar 

  • Reynolds B, Richards JB, de Wit H (2006) Acute-alcohol effects on the Experiential Discounting Task (EDT) and a question-based measure of delay discounting. Pharmacol Biochem Behav 83:194–202

    Article  CAS  PubMed  Google Scholar 

  • Richards JB, Sabol KE, de Wit H (1999) Effects of methamphetamine on the adjusting amount procedure, a model of impulsive behavior in rats. Psychopharmacology (Berlin) 146:432–439

    Article  CAS  Google Scholar 

  • Roerig SC, O’Brien SM, Fujimoto JM, Wilcox GL (1984) Tolerance to morphine analgesia: decreased multiplicative interaction between spinal and supraspinal sites. Brain Res 308:360–363

    Article  CAS  PubMed  Google Scholar 

  • Roesch MR, Takahashi Y, Gugsa N, Bissonette GB, Schoenbaum G (2007) Previous cocaine exposure makes rats hypersensitive to both delay and reward magnitude. J Neurosci 27:245–250

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schippers MC, Binnekade R, Schoffelmeer ANM, Pattij T, Vries TJ (2011) Unidirectional relationship between heroin self-administration and impulsive decision-making in rats. Psychopharmacology (Berlin) 219:443–452

    Article  Google Scholar 

  • Solinas M, Goldberg SR (2005) Motivational Effects of Cannabinoids and Opioids on Food Reinforcement Depend on Simultaneous Activation of Cannabinoid and Opioid Systems. Neuropsychopharmacology 30:2035–2045

    Article  CAS  PubMed  Google Scholar 

  • Stevens L, Verdejo-García A, Goudriaan AE, Roeyers H, Dom G, Vanderplasschen W (2014) Impulsivity as a vulnerability factor for poor addiction treatment outcomes: A review of neurocognitive findings among individuals with substance use disorders. J Subst Abuse Treat 47(1):58–72

    Article  PubMed  Google Scholar 

  • Stewart J, Badiani A (1993) Tolerance and sensitization to the behavioral effects of drugs. Behav Pharmacol 4:289

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Tanno T, Maguire DR, Henson C, France CP (2014) Effects of amphetamine and methylphenidate on delay discounting in rats: interactions with order of delay presentation. Psychopharmacology 231(1):85–95

    Article  CAS  PubMed  Google Scholar 

  • Ward RD, Odum AL (2005) Effects of morphine on temporal discrimination and color matching: General disruption of stimulus control or selective effects on timing? J Exp Anal Behav 84(3):401–415

    Article  PubMed Central  PubMed  Google Scholar 

  • Winstanley CA, LaPlant Q, Theobald DE, Green TA, Bachtell RK, Perrotti LI, DiLeone RJ, Russo SJ, Garth WJ, Self DW (2007) DeltaFosB induction in orbitofrontal cortex mediates tolerance to cocaine-induced cognitive dysfunction. J Neurosci 27:10497–10507

    Article  CAS  PubMed  Google Scholar 

  • Zacny JP, de Wit H (2009) The prescription opioid, oxycodone, does not alter behavioral measures of impulsivity in healthy volunteers. Pharmacol Biochem Behav 94(1):108–113

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zarrindast M-R, Ebrahimi-Ghiri M, Rostami P, Rezayof A (2007) Repeated pre-exposure to morphine into the ventral pallidum enhances morphine-induced place preference: involvement of dopaminergic and opioidergic mechanisms. Behav Brain Res 181:35–41

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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.

Author information

Affiliations

  1. Department of Psychology, McGill University, Montreal, QC, H3A 1B1, Canada

    Colin Harvey-Lewis & Keith B. J. Franklin

Authors
  1. Colin Harvey-Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keith B. J. Franklin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keith B. J. Franklin.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Harvey-Lewis, C., Franklin, K.B.J. The effect of acute morphine on delay discounting in dependent and non-dependent rats. Psychopharmacology 232, 885–895 (2015). https://doi.org/10.1007/s00213-014-3724-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-014-3724-x

Keywords

  • Morphine
  • Hyperalgesia
  • Abstinence
  • Drug abuse
  • Operant
  • Sensitization
  • Tolerance
  • Delay discounting
  • Drug dependence