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Psychopharmacologia

, Volume 46, Issue 1, pp 27–29 | Cite as

Impaired development of tolerance to morphine analgesia in rats with hereditary diabetes insipidus

  • D. de Wied
  • W. H. Gispen
Animal Studies

Abstract

Recently it was reported that vasopressin facilitates the development of resistance to the analgesic action of morphine. Therefore, the development of tolerance to daily administration of morphine-HCl (10 mg/kg i.p.) was studied in a series of trials on a hot plate using rats with hereditary diabetes insipidus (DI), which lack the ability to synthesize vasopressin. In contrast to heterozygous DI rats, who developed full tolerance after the fifth injection, homozygous DI rats showed a delayed development of tolerance. Substitution of HO-DI rats with either arginine-8-vasopressin (3 Μg/rat, s.c. daily) or the endocrinologically inert fragment of vasopressin desglycinamide lysine-8-vasopressin (5 Μg/100 g, s.c. daily) restored the impaired development of tolerance towards normal. The data support the notion that vasopressin is important to the development of tolerance to narcotic analgesics and that its mechanism of action is dissociated from its endocrine effect but rather resembles that of its known influence on memory consolidation.

Key words

Diabetes insipidus Morphine tolerance Vasopressin 

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References

  1. Ader, R., de Wied, D.: Effects of lysine vasopressin on passive avoidance learning. Psychon. Sci. 29, 46–48 (1972)Google Scholar
  2. Bonus, B., Gispen, W. H., de Wied, D.: Effect of lysine vasopressin and ACTH 4–10 on conditioned avoidance behavior of hypophysectomized rats. Neuroendocrinology 11, 137–143 (1973)Google Scholar
  3. Cohen, M., Keats, A. S., Krivoy, W. A., Ungar, G.: Effect of actinomycin on morphine tolerance. Proc. Soc. exp. Biol. (N.Y.) 119, 381–384 (1965)Google Scholar
  4. Cox, B. M., Osman, O. H.: Inhibition of the development of tolerance to morphine in rats by drugs which inhibit ribonucleic acid or protein synthesis. Brit. J. Pharmacol. 38, 157–170 (1970)Google Scholar
  5. De Wied, D.: Long term effect of vasopressin on the maintenance of a conditioned avoidance response in rats. Nature (Lond.) 232, 58–60 (1971)Google Scholar
  6. De Wied, D., Bohus, B., van Wimersma Greidanus Tj. B.: The hypothalamo-hypophyseal system and the preservation of conditioned avoidance behavior in rats. In: Integrative hypothalamic activity. D. F. Swaab and J. P. Schadé, eds., Progress in brain research, vol. 41, pp. 417–428. Amsterdam: Elsevier 1974Google Scholar
  7. De Wied, D., Greven, H. M., Lande, S., Witter, A.: Dissociation of the behavior and endocrine effects of lysine vasopressin by tryptic digestion. Brit. J. Pharmacol. 45, 118–122 (1972)Google Scholar
  8. Eddy, N. B., Leimbach, D.: Synthetic analgesics. II. Dithienylbutenyl- and Dithienylbutylamines. J. Pharmacol. exp. Ther. 107, 385–393 (1953)Google Scholar
  9. King, A. R., de Wied, D.: Localized behavioral effects of vasopressin on maintenance of an active avoidance response in rats. J. comp. physiol. Psychol. 86, 1008–1018 (1974)Google Scholar
  10. Krivoy, W. A., Zimmermann, E., Lande, S.: Facilitation of development of resistance to morphine analgesia by desglycinamide9-lysine-vasopressin. Proc. nat. Acad. Sci. (Wash.) 71, 1852–1856 (1974)Google Scholar
  11. Lande, S., Flexner, J. B., Flexner, L. B.: Effect of corticotropin and desglycinamide9-lysine-vasopressin on suppression of memory by puromycin. Proc. nat. Acad. Sci. (Wash.) 69, 558–560 (1972)Google Scholar
  12. Lande, S., Witter, A., de Wied, D.: Pituitary peptides. An octapeptide that stimulates conditioned avoidance acquisition in hypophysectomized rats. J. biol. Chem. 246, 2058–2062 (1971)Google Scholar
  13. Valtin, H., Schroeder, H. A.: Familial hypothalamic diabetes insipidus in rats (Brattleboro strain). Amer. J. Physiol. 206, 425–430 (1964)Google Scholar

Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • D. de Wied
    • 1
  • W. H. Gispen
    • 1
  1. 1.Rudolf Magnus Institute for Pharmacology, Medical FacultyUniversity of UtrechtUtrechtThe Netherlands

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