Revaluation of the Role of Alpha<sub>2</sub>-Adrenoreceptors in Morphine-Stimulated Release of Growth Hormone

Abstract

The relationship between opioidergic and alpha 2-adrenergic system in the regulation of GH secretion was studied using a novel alpha 2-antagonist, CH-38083, and chronic treatment with yohimbine or clonidine. In male Wistar rats morphine (3 mg/kg s.c.), and clonidine (31 micrograms/kg i.p.) induced a significant increase in plasma GH levels. The pretreatment with the alpha 2-antagonist yohimbine (1 and 3 mg/kg) effectively inhibited the GH releasing effect or morphine and clonidine. CH-38083 at the dose of 1 mg/kg did not interfere with the morphine-induced GH secretion, while it fully antagonized the GH-releasing effect of clonidine. Higher doses (3 and 5 mg/kg) of CH-38083 only partly inhibited GH secretion induced by morphine. In rats chronically treated with clonidine (2 micrograms/ml in the drinking water for 14 days) the GH response to an injection of clonidine was blocked, while the effect of morphine on the GH secretion remained unchanged. In long-term castrated rats the effect of clonidine (15, 31 and 250 micrograms/kg i.p.) on the GH secretion was significantly blunted, while the GH-releasing effect of morphine (1, 3 and 5 mg/kg s.c.) remained unchanged. The replacement of testosterone (10 mg/kg for 4 days) in castrates restored the effect of clonidine, whereas it decreased the stimulatory action of morphine on the GH secretion. In rats chronically treated with yohimbine (2 mg/kg i.p. 2-3 times daily for 14 days until sacrifice), the GH response to a high dose of clonidine (0.5 mg/kg i.p.) was blocked, while the effect of morphine (5 mg/kg s.c.) was significantly enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)