Abstract
Chlordiazepoxide (CDP) has been previously shown to possess antinociceptive properties that are resistant, except at high doses, to the opiate antagonist naloxone. The present study evaluated whether CDP's antinociceptive effects were subject to tolerance following repeated injections and whether cross-tolerance might develop between the antinociceptive action of CDP and that of either morphine or cold water swims. CDP increased flinch-jump thresholds following acute administration and exhibited tolerance following repeated injections. Neither morphine-tolerant nor cold water swim-adapted rats displayed an antinociceptive effect when tested with CDP. On the other hand, chronic pretreatment with CDP attenuated the antinociceptive effects of cold water swims, but did not produce any clear effect upon morphine analgesia.
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References
Akera, T., Brody, T. M.: The addiction cycle to narcotics in the rat and its relation to catecholamines. Biochem. Pharmacol. 17, 675–688 (1968)
Bodnar, R. J., Glusman, M., Brutus, M., Spiaggia, A., Kelly, D. D.: Analgesia induced by cold-water stress: Attenuation following hypophysectomy. Physiol. Behav. 23, 53–62 (1979a)
Bodnar, R. J., Kelly, D. D., Spiaggia, A., Ehrenberg, C., Glusman, M.: Dose-dependent reductions by naloxone of analgesia induced by cold-water stress. Pharmacol. Biochem. Behav. 8, 667–672 (1978a)
Bodnar, R. J., Kelly, D. D., Steiner, S. S., Glusman, M.: Stress-produced analgesia lack of cross-tolerance. Pharmacol. Biochem. Behav. 8, 661–666 (1978b)
Bodnar, R. J., Zimmerman, E. A., Abrams, G. M., Mansour, A., Thomas, L. W., Glusman, M.: Neonatal hypothalamic deficits reduce analgesia induced by stress and opiates. Soc. Neurosci. Abstr. 5, 605 (1979b)
Corrodi, H., Fuxe, K., Lidbrink, P., Olson, L.: Minor tranquilizers, stress and central catecholamine neurons. Brain Res. 29, 1–16 (1971)
Evans, W. O.: A new technique for the investigation of some analgeric drugs on a reflex behavior in the rat. Psychopharmacology 2, 318–325 (1961)
File, S. E., Vellucci, S. V.: Studies on the role of ACTH and 5-HT in anxiety, using an animal model. J. Pharm. Pharmacol. 30, 105–119 (1978)
Glusman, M., Bodnar, R. J., Kelly, D. D., Sirio, C., Stern, J., Zimmerman, E. A.: Attenuation of stress-induced analgesia by anterior hypophysectomy in the rat. Soc. Neurosci. Abstr. 5, 609 (1979)
Grotto, M., Sulman, F. G.: Interaction of analgesic effects of psychopharmaca. Arch. Int. Pharmacodyn. Ther. 170, 257–263 (1967)
Gupta, S. K., Gaitonde, B. B.: Analgesic activity of a new quinoline derivative RO-4-1778. Indian J. Physiol. Pharmacol. 7, 27–32 (1964)
Houser, V., Pare, W.: Analgesic potency of sodium salicylate, indomethacin, and chlordiazepoxide as measured by the spatial preference technique in the rat. Psychopharmacology 32, 121–131 (1973)
Kelly, D. D., Bodnar, R. J., Brutus, M., Woods, C. F., Glusman, M.: Differential effects upon liminal-escape pain thresholds by neuroleptic, antidepressant and anxiolytic agents. Fed. Proc. 37, 470 (1978a)
Kelly, D. D., Brutus, M., Bodnar, R. J.: Differential effects of naloxone upon elevations in liminal escape pain thresholds induced by psychotropic drugs: Reversal of chlordiazepoxide but enhancement of neuroleptic analgesia. Proc. Int. Cong. Pharmacol. 7, 119 (1978b)
Lahti, R. A., Barsuh, C.: On the effect of minor tranquilizers on stress-induced increases in rat plasma corticosterone. Psychopharmacology 35, 215–220 (1974)
Lord, J. A. H., Waterfield, A. A., Hughes, J., Kosterlitz, H. W.: Endogenous opioid peptides: Multiple agonists and receptors. Nature 267, 495–499 (1977)
Margules, D. L., Stein, L.: Increase of antianxiety activity and tolerance of behavioral depression during chronic administration of oxazepam. Psychopharmacology 13, 74–80 (1968)
Martin, W. R.: Opioid antagonist. Pharmacol. Rev. 198, 463–521 (1967)
Schenberg, L. C., Graeff, F. G.: Role of the periaqueductal gray substance in the antianxiety action of benzodiazepines. Pharmacol. Biochem. Behav. 9, 287–295 (1978)
Selye, H.: The story of the adaptation syndrome. Montreal: Acta 1952
Shannon, H. E., Holtzman, S. G., Davis, D. C.: Interactions between narcotic analgesics and benzodiazepine derivatives on behavior in the mouse. J. Pharmacol. Exp. Ther. 199, 389–399 (1976)
Stone, E. A.: Swim-stress-induced inactivity: Relation to body temperature and brain norepinephrine, and effects of d-amphetamine. Psychosom. Med. 32, 51–59 (1970)
Taylor, K. M., Laverty, R.: The interaction of chlordiazepoxide, diazepam and nitrazepam with catecholamines and histamine in regions of the rat brain. In: The benzodiazepines, S. Garattini, E. Mussini, eds. New York: Raven 1973
Taylor, K. M., Snyder, S. H.: Brain histamine: Rapid apparent turnover altered by restraint and cold stress. Science 172, 1037–1039 (1971)
Vellucci, S. V., File, S. E.: Chlordiazepoxide loses its anxiolytic action with long-term treatment. Psychopharmacology 62, 61–65 (1979)
Warner, R. S.: Management of the office patient with anxiety and depression. Psychosomatics 6, 347–351 (1965)
Weiss, J.: Morphine antagonistic effect of chlordiazepoxide (Librium). Experientia 25, 381 (1969)
Weller, C. P., Ibrahim, I., Sulman, F. G.: Analgesic profile of tranquilizers in multiple screening tests in mice. Arch. Int. Pharmacodyn. Ther. 176, 176–192 (1968)
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Bodnar, R.J., Kelly, D.D., Thomas, L.W. et al. Chlordiazepoxide antinociception: Cross-tolerance with opiates and with stress. Psychopharmacology 69, 107–110 (1980). https://doi.org/10.1007/BF00426530
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DOI: https://doi.org/10.1007/BF00426530