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Psychopharmacology

, Volume 104, Issue 2, pp 181–186 | Cite as

Tolerance to the analgesic, but not discriminative stimulus effects of morphine after brief social defeat in rats

  • Klaus A. Miczek
Original Investigations

Abstract

One of the most prominent consequences of defeat in a social confrontation is a long-lasting tolerance-like insensitivity to the analgesic effects of opiates, even when only small short-lived changes in nociception are detectable during the acute social stress. The present experiments examined (1) which kinds of social experiences lead to morphine tolerance, (2) whether or not the morphine tolerance in defeat-experienced rats extends from the analgesic effects to the discriminative stimulus and rate-decreasing effects of morphine, and (3) how long morphine tolerance lasts after a defeat experience. After five brief social confrontations including attack and threat by a resident rat leading to submission or defeat of the intruder, the latter exhibits marked tolerance to the analgesic effects of morphine, but not to the discriminative stimulus or behaviorally suppressive effects. Changes in social housing did not alter morphine's behavioral effects. Tolerance to the analgesic morphine effects was detected for 2 months after the defeat experience, whereas the discriminative stimulus and rate-decreasing effects were closely similar to those before defeat. This pattern was seen in animals for whom discriminative stimulus training with morphine was suspended after defeat as well as in those for whom it continued. In additional defeated and non-defeated animals, morphine's effects on the acoustic startle reflex was assessed. In contrast to the tail flick reflex to a noxious heat stimulus, the acoustic startle response remained unaffected by defeat experience or by morphine (up to 30 mg/kg). The long-lasting and large degree of tolerance after brief social defeat experiences appears to be limited to the analgesic effects of morphine. Whether or not endogenous opioid peptide activity during the actual defeat may substitute for the morphine stimulus remains to be established.

Key words

Opiates Tolerance Aggression Defeat Pain Analgesia Reinforcement schedules Drug discrimination Startle 

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References

  1. Appelbaum BD, Holtzman SG (1984) Characterization of stress-induced potentiation of opioid effects in the rat. J Pharmacol Exp Ther 231:555–565Google Scholar
  2. Appelbaum BD, Holtzman SG (1985) Restraint stress enhances morphine-induced analgesia in the rat without changing apparent affinity of receptor. Life Sci 36:1069–1074Google Scholar
  3. Appelbaum BD, Holtzman SG (1986) Stress-induced changes in the analgesic and thermic effects of opioid peptides in the rat. Brain Res 377:330–336Google Scholar
  4. Colpaert FC (1978) Discriminative stimulus properties of narcotic analgesic drugs. Pharmacol Biochem Behav 9:863–887Google Scholar
  5. Colpaert FC, Kuyps JJ, Niemegeers CJE, Janssen PAJ (1976) Discriminative stimulus properties of fentanyl and morphine: tolerance and dependence. Pharmacol Biochem Behav 5:401–408Google Scholar
  6. D'Amour FE, Smith DL (1941) A method for determining loss of pain sensation. J Pharmacol Exp Ther 72:74–79Google Scholar
  7. Davis M (1979) Morphine and naloxone: Effects on conditioned fear as measured with the potentiated startle paradigm. Eur J Pharmacol 54:341–347Google Scholar
  8. Dewey WL, Harris LS (1975) The tail-flick test. In: Ehrenpreis S, Neidle A (eds) Methods in narcotics research. Marcel Dekker, New York, pp 101–109Google Scholar
  9. Emmett-Oglesby MW, Shippenberg TS, Herz A (1988) Tolerance and cross-tolerance to the discriminative stimulus properties of fentanyl and morphine. J Pharmacol Exp Ther 245:17–23Google Scholar
  10. Jaffe JH (1985) Drug addiction and drug abuse. In: Gilman A, Goodman LS, Rall TW, Murad F (eds), Goodman and Gilman's the pharmacological basis of therapeutics. MacMillan, New York, pp 532–581Google Scholar
  11. Krimmer EC, McGuire MS, Barry H III (1984) Effects of the training dose on generalization of morphine stimulus to clonidine. Pharmacol Biochem Behav 20:669–673Google Scholar
  12. Külling P, Frischknecht HR, Pasi A, Waser PG, Siegfried B (1987) Effects of repeated as compared to single aggressive confrontation on nociception and defense behavior in C57BL/6 and DBA/2 mice. Physiol Behav 39:01–07Google Scholar
  13. Miczek KA (1979) A new test for aggression in rats without aversive stimulation: differential effects ofd-amphetamine and cocaine. Psychopharmacology 60:253–259Google Scholar
  14. Miczek KA, Winslow JT (1987) Analgesia and decrement in operant performance in socially defeated mice: Selective cross-tolerance to morphine and antagonism by naltrexone. Psychopharmacology 92:444–451Google Scholar
  15. Miczek KA, Thompson ML (1984) Analgesia resulting from defeat in a social confrontation: The role of endogenous opioids in brain. In: Bandler R (ed) Modulation of sensorimotor activity during altered behavioural states. Alan R. Liss, New York, pp 431–456Google Scholar
  16. Miczek KA, Thompson ML, Shuster L (1982) Opioid-like analgesia in defeated mice. Science 215:1520–1522Google Scholar
  17. Miczek KA, Thompson ML, Shuster L (1985) Naloxone injections into periaqueductal grey area and arcuate nucleus block analgesia in defeated mice. Psychopharmacology 87:39–42Google Scholar
  18. Miczek KA, Thompson ML, Tornatzky W (1991) Subordinate animals: behavioral and physiological adaptations and opioid tolerance. In: Brown MR, Rivier C, Koob G (eds) Neurobiology and neuroendocrinology of stress. Marcel Dekker, New York (in press)Google Scholar
  19. Overton DA (1979) Drug discrimination training with progressively lowered doses. Science 205:720–721Google Scholar
  20. Rodgers RJ, Hendry CA (1983) Social conflict activates status-dependent endogenous analgesic or hyperalgesic mechanisms in male mice: effects of naloxone on nociception and behaviour. Physiol Behav 30:775–780Google Scholar
  21. Rodgers RJ, Randall JI (1985) Social conflict analgesia: studies on naloxone antagonism and morphine cross-tolerance in male DBA/2 mice. Pharmacol Biochem Behav 23:883–887Google Scholar
  22. Sannerud CA, Young AM (1987) Environmental modification of tolerance to morphine discriminative stimulus properties in rats. Psychopharmacology 93:59–68Google Scholar
  23. Thompson ML, Kream RM (1991) Social conflict alters brain opioid mechanisms in mice. Eur J Pharmacol (submitted)Google Scholar
  24. Vellucci SV, Martin PJ, Everitt BJ (1988) The discriminative stimulus produced by pentylenetetrazol: effects of systemic anxiolytics and anxiogenics, aggressive defeat and midazolam or muscimol infused into the amygdala. J Psychopharmacol 2:80–93Google Scholar
  25. Warren PH, Ison JR (1982) Selective action of morphine on reflex expression to nociceptive stimulation in the rat: a contribution to the assessment of analgesia. Pharmacol Biochem Behav 16:869–874Google Scholar
  26. Wenger GR (1980) Cumulative dose-response curves in behavioral pharmacology. Pharmacol Biochem Behav 13:647–651Google Scholar
  27. Young AM, Sannerud CA (1989) Tolerance to drug discriminative stimuli. In: Goudie AJ, Emmett-Oglesby M (eds) Psychoactive drugs. Humana Press, Clifton, NJ, pp 221–278Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Klaus A. Miczek
    • 1
  1. 1.Department of PsychologyTufts UniversityMedfordUSA

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