Corticosteroid effects on morphine-induced antinociception as a function of two types of corticosteroid receptors in brain.
The antinociceptive effect of parenterally and intracerebroventricularly injected morphine and beta-endorphin in adrenalectomized rats and in adrenalectomized rats treated with adrenal steroids was examined employing the hot-plate method. (1) Adrenalectomy sensitized the rats to an analgesic effect of morphine and beta-endorphin. (2) Replacement therapy (chronic and acute) with corticosterone, dexamethasone or RU 28362 (glucocorticoid receptor agonist) effectively reversed the increase in the sensitivity to the analgesic effect of peripherally injected morphine (5 mg/kg i.p.) induced by adrenalectomy to the level of sham-operated animals. Glucocorticosteroids administered to non-adrenalectomized rats did not change the sensitivity to morphine. (3) Corticosterone had a biphasic, dose-dependent effect; the most significant attenuation of the hypersensitivity to morphine-induced antinociception in adrenalectomized rats was achieved after 0.01 mg and after 10 mg (per kg b.w.). Doses of corticosterone of 0.005 mg/kg and in a range of 0.05-0.30 mg/kg were ineffective. (4) Corticosterone in a dose of 0.01 mg/kg (s.c.) had suppressant effects on the adrenalectomy-induced increase in the sensitivity to antinociception induced by morphine when given prior to morphine (60, 30 and 5 min) as well as after the injection of morphine (before the first and the second testing on the hot-plate, 15 and 5 min, respectively). (5) Intracerebroventricularly (i.c.v.) injected morphine and beta-endorphin also displayed the hypersensitivity to the analgesic effect in adrenalectomized rats which in both cases could be suppressed by 0.01 mg/kg of corticosterone given subcutaneously 5 min prior to administration of the opiate.(ABSTRACT TRUNCATED AT 250 WORDS)
Ratka
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A
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
Veldhuis
H D
HD
De Kloet
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ER
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000315:Adrenalectomy; D000698:Analgesia; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000145:classification / Q000187:drug effects*; D001615:beta-Endorphin / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D011965:Receptors, Glucocorticoid; D001615:beta-Endorphin; D009020:Morphine