Abstract
During a social confrontation between a resident and an intruder mouse, only the submissive or defeated intruder shows an opioid-mediated analgesia to which tolerance develops. We investigated the altered morphine responsiveness after different kinds of social experiences. Mice were assessed for performance of operant behavior under the control of a fixed ratio schedule of positive reinforcement as well as for the tail flick response to a heat stimulus before and after one or five consecutive social confrontations. The dose-effect curves for morphine's suppression of schedule-controlled behavior were closely similar before and after defeat in a single or in five social confrontations. However, the concurrently measured response to pain in the tail flick assay produced morphine dose-effect curves that were shifted to the right after defeat in one or five social confrontations. Four to six times higher doses of morphine were necessary to produce analgesia in mice that were defeated in five social confrontations. Naltrexone (1 mg/kg, ip) antagonized the suppressive effects of morphine (10 mg/kg, ip) on rate of responding and the analgesic effects. Naltrexone also blocked the development of analgesia in mice that were defeated for the first time in a social confrontation, but did not prevent the suppressive effects on rate of responding. Specific social experiences such as defeat in a social confrontation appear to alter endogenous opioid process that mediate analgesia; these processes differ from those that suppress positively reinforced behavior. The differential development of morphine tolerance to the analgesic effects, but not the rate-decreasing effects as well as the differential naltrexone antagonism of both effects may indicate the involvement of opioid and non-opioid mechanisms.
Similar content being viewed by others
References
D'Amour FE, Smith DL (1941) A method for determining loss of pain sensation. J Pharmacol Exp Ther 72:74–79
Ferster CB, Skinner BF (1957) Schedules of reinforcement. Appleton-Century-Crofts, New York
Frischknecht HR, Siegfried B, Waser PG (1986) Experience modifies low intensity social conflict analgesia in mice. Psychopharmacology 89:S 15
Ginsburg B, Allee WC (1942) Some effects of conditioning on social dominance and subordination in inbred strains of mice. Physiol Zool 15:485–506
Huckledbridge FH, Nowell NW (1973) Inhibition of adrenal medullary response to fighting in subordinate and chronically defeated mice. J Endocrinol 57:37–38
Kelly DD (ed) (1986) Stress-induced analgesia. Ann NY Acad Sci Vol. 467
Kornetsky C, Bain G (1968) Morphine: Single-dose tolerance. Science 162:1011–1012
Leshner AI (1981) The role of hormones in the control of submissiveness. In: Brain PF, Benton DA (eds) A multidisciplinary approach to aggression research. Elsevier, Amsterdam, pp 309–322
Leshner AI (1983) The hormonal responses to competition and their behavioral significance. In: Svare BB (ed) Hormones and aggressive behavior. Plenum, New York, pp 393–404
Lewis JW, Cannon JT, Liebeskind JC (1980) Opioid and nonopioid mechanisms of stress analgesia. Science 298:623–625
Miczek KA (1986) Functionally specific tolerance to opioid agonists after social defeat: Analgesia and operant performance. Soc Neurosci Abstr 12:411
Miczek KA, O'Donnell JM (1978) Intruder-evoked aggression in isolated and nonisolated mice: Effects of psychomotor stimulants and L-dopa. Psychopharmacology 57:47–55
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. Liss, New York, pp 431–456
Miczek KA, Winslow JT (1987) Psychopharmacological research on aggressive behavior. In: Greenshaw A, Dourish C (eds) Experimental psychopharmacology, Humana, Clifton, NJ
Miczek KA, Thompson ML, Shuster L (1982) Opioid-like analgesia in defeated mice. Science 215:1520–1522
Miczek KA, Thompson ML, Shuster L (1985) Naloxone injections into periaqueductal grey area and arcuate nucleus block analgesia in defeated mice. Psychopharmacology 87:39–42
Miczek KA, Thompson ML, Shuster L (1986) Analgesia following defeat in an aggressive encounter: Development of tolerance and changes in opioid receptors. In: Kelly DD (ed) Stress-induced analgesia. Ann NY Acad Sci 467:14–29
Rodgers RJ, Hendrie CA (1983) Social conflict activates statusdependent endogenous analgesic or hyperalgesic mechanisms in male mice: Effects of naloxone on nociception and behaviour. Physiol Behav 30:775–780
Rodgers RJ, Randall JI (1985) Social conflict analgesia: Studies on naloxone antagonism and morphine cross-tolerance in male DBA/2 mice. Pharmacol Biochem Behav 23:883–887
Shuster L (1975) Genetic analysis of morphine effects: Activity, analgesia, tolerance and sensitization. In: Eleftheriou BE (ed) Psychopharmacogenetics. Plenum, New York, pp 73–98
Show AE, Dewey WL (1983) A comparison of antiociception induced by foot shock and morphine. J Pharmacol Exp Ther 227:42–50
Terman GW, Shavit Y, Lewis JW, Cannon JT, Liebeskind JC (1984) Intrinsic mechanisms of pain inhibition: Activated by stress. Science 226:1270–1277
Teskey GC, Kavaliers M, Hirst M (1984) Social conflict activates opioid analgesic and ingestive behaviors in male mice. Life Sci 35:303–315
Thompson ML, Brunner E, Hoefler H, Hartley J, Kumar MSA, Shuster L, Kream R (1986) Changes in opioid receptor binding and levels of opioid peptides in the brain following acute and chronic defeat in mice. Soc Neurosci Abstr 12:411
Thompson ML, Miczek KA, Noda K, Schuster L, Kumar MSA (1987) Analgesia in defeated mice: Evidence for mediation via central rather than pituitary or adrenal endogenous opioid peptides. Pharmacol Biochem Behav (in press)
Watkins LR, Mayer DJ (1982) Organization of endogenous opiate and nonopiate pain control systems. Science 216:1185–1192
Wenger GR, Dews PB (1976) The effects of phencyclidine, ketamine, d-amphetamine and pentobarbitol on schedule-controlled behavior in the mouse. J Pharmacol Exp Ther 196:616–624
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miczek, K.A., Winslow, J.T. Analgesia and decrement in operant performance in socially defeated mice: Selective cross-tolerance to morphine and antagonism by naltrexone. Psychopharmacology 92, 444–451 (1987). https://doi.org/10.1007/BF00176476
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00176476