, Volume 82, Issue 3, pp 241–247 | Cite as

Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination

  • R. F. Mucha
  • S. D. Iversen
Original Investigations


In rats, conditioned place preferences are produced by morphine and conditioned place aversions produced by naloxone. In the present studies, several issues concerning the demonstration and interpretation of place conditioning findings were examined in a two-compartment (black and white) tilt box: (1) the responses of naive rats to testing, (2) place conditioning in rats with strong unconditioned biases to one of the sides, and (3) modifications of the testing situation so that naive rats respond to the black and white sides with a minimum of initial bias. Experiments involving manipulation of the conditions of training and testing, use of pentobarbital, and use of a three-compartment test box helped to control for morphine's ability to produce state dependent learning as an explanation of its conditioned place preference. In addition, we examined previous place conditioning studies that failed to show aversive effects of naloxone. These negative findings were suggested to be due to the use or procedures insensitive to aversive stimuli and to the IP administration of naloxone. Finally, in the course of the experiments, novel data on general parameters of the place conditioning were provided. Dose-response curves for subcutaneous (SC) morphine (0.04–5.0 mg/kg) and naloxone (0.02–5.0 mg/kg) were established. Conditioned preferences were also shown to occur after at three pairings of SC drug, and they were retained for at least 1 month.

Key words

Opiates Morphine Naloxone Conditioned place preference Reward Reinforcement State-dependent learning Rat 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Berlyne DE (1969) The reward value of indifferent stimulation. In: Tapp JT (ed) Reinforcement and behavior. Academic Press, New York, pp 179–214Google Scholar
  2. Bozarth MA, Wise RA (1981) Heroin reward is dependent on a dopaminergic substrate. Life Sci 29:1881–1886Google Scholar
  3. Downs DA, Woods JA (1976) Naloxone as a negative reinforcer in rhesus monkeys: effect of dose, schedule, and narcotic regimen. Pharmacol Rev 27:397–436Google Scholar
  4. Kamin LJ (1969) Predictability, surprise, attention, and conditioning. In: Campbell BA, Church RM (eds) Punishment and averise behavior. Appleton-Century-Crofts, New York, pp 279–296Google Scholar
  5. Katz RJ, Gormezano G (1979) A rapid and inexpensive technique for assessing the reinforcing effects of opiate drugs. Pharmacol Biochem Behav 10:397–405Google Scholar
  6. Kumar R (1972) Morphine dependence in rats: Secondary reinforcements from environmental stimuli. Psychopharmacology 60:59–65Google Scholar
  7. Lukas G, Brindle SD, Greengard P (1971) The route of absorption of intraperitoneally-administered compounds. J Pharmacol Exp Ther 178:562–566Google Scholar
  8. Mucha RF, van der Kooy D, O'Shaughnessy M, Bucenieks P (1982) Drug reinforcement studied by use of place conditioning in rat. Brain Res 243:91–105Google Scholar
  9. Mucha RF, Volkovskis C, Kalant H (1981) Conditioned increases in locomotor activity produced with morphine as an unconditioned stimulus, and the relation of conditioning to acute morphine effect and tolerance. J Comp Physiol Psychol 95:351–362Google Scholar
  10. Overton DA (1964) State-dependent or “dissociated” learning produced with pentobarbital. J Comp Physiol Psychol 57:3–12Google Scholar
  11. Overton DA (1973) State-dependent learning produced by addicting drugs. In: Fisher S, Freedman AM (eds) Opiate addiction: Origins and treatments. Winston, Washington, pp 61–75Google Scholar
  12. Phillips AG, LePiane FG (1980) Reinforcing effects of morphine microinjection into the ventral tegmental area. Pharmacol Biochem Behav 12:965–968Google Scholar
  13. Phillips AG, LePiane FG (1982) Reward produced by microinjection of (d-Ala2), Met5-enkephalinamide into the ventral tegmental area. Behav Brain Res 5:225–229Google Scholar
  14. Rossi NA, Reid LD (1976) Affective states associated with morphine injections. Physiol Psychol 4:269–274Google Scholar
  15. Sherman JF, Pickman C, Rice A, Liebeskind JC, Holman EW (1980) Rewarding and aversive effects of morphine: temporal and pharmacological properties. Pharmacol Biochem Behav 13:501–505Google Scholar
  16. Stolerman I, Pilcher CW, D'Mello GD (1978) Stereospecific aversive property of narcotic antagonists in morphine-free rats. Life Sci 22:1755–1762Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • R. F. Mucha
    • 1
  • S. D. Iversen
    • 1
  1. 1.Department of Experimental PsychologyUniversity of CambridgeCambridgeUK

Personalised recommendations