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.
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References
Ader, R., de Wied, D.: Effects of lysine vasopressin on passive avoidance learning. Psychon. Sci. 29, 46–48 (1972)
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)
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)
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)
De Wied, D.: Long term effect of vasopressin on the maintenance of a conditioned avoidance response in rats. Nature (Lond.) 232, 58–60 (1971)
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 1974
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)
Eddy, N. B., Leimbach, D.: Synthetic analgesics. II. Dithienylbutenyl- and Dithienylbutylamines. J. Pharmacol. exp. Ther. 107, 385–393 (1953)
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)
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)
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)
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)
Valtin, H., Schroeder, H. A.: Familial hypothalamic diabetes insipidus in rats (Brattleboro strain). Amer. J. Physiol. 206, 425–430 (1964)
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de Wied, D., Gispen, W.H. Impaired development of tolerance to morphine analgesia in rats with hereditary diabetes insipidus. Psychopharmacologia 46, 27–29 (1976). https://doi.org/10.1007/BF00421545
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DOI: https://doi.org/10.1007/BF00421545