Skip to main content
SpringerLink
Log in

Effects of morphine and naltrexone on impulsive decision making in rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

It has been reported that human opiate addicts discount delayed rewards more than non-addicts, indicating that they are more impulsive. However, it is not clear whether this difference reflects pre-existing traits, or the effects of exposure to the opiates.

Objectives

This study was designed to investigate the effects of an opioid agonist and antagonist on delay discounting in rats. The study had three objectives: to determine (1) the acute effects of the opioid agonist morphine (MOR) on delay discounting, (2) the acute effects of the opioid antagonist naltrexone (NAL) on delay discounting, and (3) whether NAL reverses the effects of MOR on delay discounting.

Methods

An adjusting amount procedure (AdjAmt) was used to determine how much animals discounted the value of delayed rewards. Acute doses of MOR (0.3, 1.0, and 1.8 mg/kg SC), NAL (0.01, 0.1, 1.0, and 10 mg/kg SC) and NAL (0.1 mg/kg SC) prior to MOR (1.8 mg/kg SC) were tested in 15 rats.

Results

MOR dose dependently increased the rate of delay discounting (i.e., made the animals more impulsive). NAL alone had no effect on the value of delayed rewards, but NAL blocked the effects of MOR.

Conclusions

These results suggested that the direct effects of MOR may contribute to the high level of impulsive behavior seen among opiate users.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ainslie G (1975) Specious reward: a behavioral theory of impulsiveness and impulse control. Psychol Bull 82:463–496

    CAS  PubMed  Google Scholar 

  • Berridge KC (1996) Food reward: brain substrates of wanting and liking. Neurosci Biobehav Rev 20:1–25

    CAS  PubMed  Google Scholar 

  • Brown DR, Holtzman SG (1979) Suppression of deprivation-induced food and water intake in rats and mice by naloxone. Pharmacol Biochem Behav 11:567–573

    Article  CAS  PubMed  Google Scholar 

  • Brown DR, Blank MS, Holtzman SG (1980) Suppression by naloxone of water intake induced by deprivation and hypertonic saline in intact and hypophysectomized rats. Life Sci 26:1535–1542

    Article  CAS  PubMed  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 152:362–375

    CAS  PubMed  Google Scholar 

  • Castellano C, Puglisi-Allegra S (1982) Effects of naloxone and naltrexone on locomotor activity in C57BL/6 and DBA/2 mice. Pharmacol Biochem Behav 16:561–563

    Article  CAS  PubMed  Google Scholar 

  • De Oliveira RW, Nakamura-Palacios EM (2003) Haloperidol increases the disruptive effect of alcohol on spatial working memory in rats: a dopaminergic modulation in the medial prefrontal cortex. Psychopharmacology 170:51–61

    Article  PubMed  Google Scholar 

  • Di Chiara G, Imperato A (1988) Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. J Pharmacol Exp Ther 244:1067–1080

    PubMed  Google Scholar 

  • Evenden JL, Ryan CN (1996) The pharmacology of impulsive behaviour in rats: the effects of drugs on response choice with varying delays of reinforcement. Psychopharmacology 128:161–170

    Google Scholar 

  • Finn PR, Justus A, Mazas C, Steinmetz JE (1999) Working memory, executive processes and the effects of alcohol on go/no-go learning: testing a model of behavioral regulation and impulsivity. Psychopharmacology 146:465–472

    Google Scholar 

  • Giordano LA, Bickel WK, Loewenstein G, Jacobs EA, Marsch L, Badger GJ (2002) Mild opiate deprivation increases the degree that opioid-dependent outpatients discount delayed heroin and money. Psychopharmacology 163:174–182

    Article  CAS  PubMed  Google Scholar 

  • Grace RC (1999) The matching law and amount-dependent exponential discounting as accounts of self-control choice. J Exp Anal Behav 71:27–44

    Google Scholar 

  • Green L, Myerson J, McFadden E (1997) Rate of temporal discounting decreases with amount of reward. Mem Cognit 25:715–723

    CAS  PubMed  Google Scholar 

  • Herrnstein RJ (1981) Self-control as response strength. In: Bradshaw CM, Szabadi E, Lowe CF (eds) Quantification of steady-state operant behavior. Elsevier, Amsterdam, pp 3–20

  • Hinson JM, Jameson TL, Whitney P (2003) Impulsive decision making and working memory. J Exp Psychol Learn Mem Cogn 29:298–306

    Article  PubMed  Google Scholar 

  • Itoh J, Ukai M, Kameyama T (1994) Dynorphin A-(1–13) potently improves the impairment of spontaneous alternation performance induced by the mu-selective opioid receptor agonist DAMGO in mice. J Pharmacol Exp Ther 269:15–21

    CAS  PubMed  Google Scholar 

  • Iwamoto ET (1984) An assessment of the spontaneous activity of rats administered morphine, phencyclidine, or nicotine using automated and observational methods. Psychopharmacology 84:374–382

    CAS  PubMed  Google Scholar 

  • Johnson MW, Bickel WK (2002) Within-subject comparison of real and hypothetical money rewards in delay discounting. J Exp Anal Behav 77:129–146

    PubMed  Google Scholar 

  • 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 128:78–87

    CAS  PubMed  Google Scholar 

  • Koek W, Slangen JL (1984) Acute effects of naloxone and naltrexone, but lack of delayed effects, on exploratory behavior in the rat. Psychopharmacology 84:383–387

    CAS  PubMed  Google Scholar 

  • Kuzmin A, Sandin J, Terenius L, Ogren SO (2000) Dose- and time-dependent bimodal effects of kappa-opioid agonists on locomotor activity in mice. J Pharmacol Exp Ther 295:1031–1042

    CAS  PubMed  Google Scholar 

  • Logue AW (1988) Research on self-control: an integrated framework. Behav Brain Sci 11:665–709

    Google Scholar 

  • Luce RD (1986) Response times: their role in inferring elementary mental organization. Oxford University Press, New York

    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 participants: drug and monetary rewards. Exp Clin Psychopharmacol 5:256–262

    CAS  PubMed  Google Scholar 

  • Madden GJ, Bickel WK, Jacobs EA (1999) Discounting of delayed rewards in opioid-dependent outpatients: exponential or hyperbolic discounting functions? Exp Clin Psychopharmacol 7:284–293

    CAS  PubMed  Google Scholar 

  • Martin WR (1967) Opioid antagonists. Pharmacol Rev 19:463–521

    CAS  PubMed  Google Scholar 

  • McMillan DE (1973) Effects of narcotics and narcotic antagonists on operant behavior. Adv Biochem Psychopharmacol 8:345–359

    CAS  PubMed  Google Scholar 

  • Molinengo L (1964) Effects of morphine on the operant behaviour in rats. Psychopharmacologia 6:347–367

    CAS  PubMed  Google Scholar 

  • Oas P (1985) The psychological asses2ment of impulsivity: a reveiw. J Psychoedu Assess 3:141–156

    Google Scholar 

  • Odum AL, Schaal DW (2000) The effects of morphine on fixed-interval patterning and temporal discrimination. J Exp Anal Behav 74:229–243

    CAS  PubMed  Google Scholar 

  • Odum AL, Madden GJ, Badger GJ, Bickel WK (2000) Needle sharing in opioid-dependent outpatients: psychological processes underlying risk. Drug Alcohol Depend 60:259–266

    CAS  PubMed  Google Scholar 

  • Pan ZZ (1998) mu-Opposing actions of the kappa-opioid receptor. Trends Pharmacol Sci 19:94–98

    Article  CAS  PubMed  Google Scholar 

  • Petry NM (2001) Delay discounting of money and alcohol in actively using alcoholics, currently abstinent alcoholics, and controls. Psychopharmacology 154:243–250

    CAS  PubMed  Google Scholar 

  • Powell KJ, Abul-Husn NS, Jhamandas A, Olmstead MC, Beninger RJ, Jhamandas K (2002) Paradoxical effects of the opioid antagonist naltrexone on morphine analgesia, tolerance, and reward in rats. J Pharmacol Exp Ther 300:588–596

    Article  CAS  PubMed  Google Scholar 

  • Rachlin H (1989) Judgment, decision, and choice: a cognitive/behavioral synthesis. W.H. Freeman and Company, New York

  • Rachlin H, Green L (1972) Commitment, choice and self-control. J Exp Anal Behav 17:15–22

    Google Scholar 

  • Rachlin H, Raineri A, Cross D (1991) Subjective probability and delay. J Exp Anal Behav 55:233–244

    CAS  PubMed  Google Scholar 

  • Rada P, Mark GP, Pothos E, Hoebel BG (1991) Systemic morphine simultaneously decreases extracellular acetylcholine and increases dopamine in the nucleus accumbens of freely moving rats. Neuropharmacology 30:1133–1136

    CAS  PubMed  Google Scholar 

  • Richards JB, Mitchell SH, de Wit H, Seiden LS (1997) Determination of discount functions in rats with an adjusting-amount procedure. J Exp Anal Behav 67:353–366

    CAS  PubMed  Google Scholar 

  • Richards JB, Sabol KE, de Wit H (1999a) Effects of methamphetamine on the adjusting amount procedure, a model of impulsive behavior in rats. Psychopharmacology (Berl) 146:432–9

    Google Scholar 

  • Richards JB, Zhang L, Mitchell SH, de Wit H (1999b) Delay or probability discounting in a model of impulsive behavior: effect of alcohol. J Exp Anal Behav 71:121–143

    CAS  PubMed  Google Scholar 

  • Sawaguchi T (2000) The role of D1-dopamine receptors in working memory-guided movements mediated by frontal cortical areas. 7:9–19

  • Sawaguchi T, Goldman-Rakic PS (1991) D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science 251:947–950

    CAS  PubMed  Google Scholar 

  • Sawaguchi T, Goldman-Rakic PS (1994) The role of D1-dopamine receptor in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response task. J Neurophysiol 71:515–528

    CAS  PubMed  Google Scholar 

  • Silva MT, Heyman GM (2001) Chronic morphine consumption decreases wheel running and wheel running-reinforced behavior in rats. Pharmacol Biochem Behav 69:51–57

    Article  CAS  PubMed  Google Scholar 

  • Uhl GR, Childers S, Pasternak G (1994) An opiate-receptor gene family reunion. Trends Neurosci 17:89–93

    Article  CAS  PubMed  Google Scholar 

  • Vasko MR, Domino EF (1978) Tolerance development to the biphasic effects of morphine on locomotor activity and brain acetylcholine in the rat. J Pharmacol Exp Ther 207:848–858

    Google Scholar 

  • Wade TR, de Wit H, Richards JB (2000) Effects of dopaminergic drugs on delayed reward as a measure of impulsive behavior in rats. Psychopharmacology 150:90–101

    Google Scholar 

  • White DA, Holtzman SG (2001) Acute opioid pretreatment potentiates naltrexone-induced drinking suppression in water-deprived rats. J Pharmacol Exp Ther 298:156–164

    Google Scholar 

  • Wise RA, Leone P, Rivest R, Leeb K (1995) Elevations of nucleus accumbens dopamine and DOPAC levels during intravenous heroin self-administration. Synapse 21:140–148

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Mark Kogutowski for technical assistance and Dr. Jerrold Winter for his helpful advice. The National Institute on Drug Abuse (DA-10588) supported this research.

Author information

Authors and Affiliations

  1. Division of Behavioral Medicine, Farber Hall, Room G56, Building no. 26, University at Buffalo, The State University of New York, 3435 Main Street, Buffalo, NY 14214-3000, USA

    Artur K. Kieres, Kathryn A. Hausknecht, Andrew M. Farrar, Ashley Acheson & Jerry B. Richards

  2. Department of Psychiatry, The University of Chicago, MC3077, 5841 S. Maryland Avenue, Chicago, IL 60637, USA

    Harriet de Wit

Authors
  1. Artur K. Kieres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathryn A. Hausknecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew M. Farrar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ashley Acheson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Harriet de Wit
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jerry B. Richards
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jerry B. Richards.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kieres, A.K., Hausknecht, K.A., Farrar, A.M. et al. Effects of morphine and naltrexone on impulsive decision making in rats. Psychopharmacology 173, 167–174 (2004). https://doi.org/10.1007/s00213-003-1697-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-003-1697-2

Keywords

Search

Navigation