Involvement of kappa-opioid receptor mechanisms in the calcitonin-induced potentiation of opioid effects at the hypothalamus-pituitary-adrenocortical axis.

The present study was conducted to evaluate the influence of calcitonin on the neuroendocrine effects of both the mu-opioid receptor agonist, morphine, and the selective kappa-opioid receptor agonist, U-50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidynyl)cyclohexyl]benzeneacetamide methane sulphonate), at the hypothalamus-pituitary-adrenocortical axis in rats. Calcitonin given alone (2.5, 5 or 10 UI/kg i.p.) induced no changes or a slight reduction (20 UI/kg i.p.) in plasma corticosterone, 45 min after its administration. Morphine did not produce any modification in plasma corticosterone at doses of 3 or 10 mg/kg i.p., whereas it produced a significant increase in corticosterone secretion at doses of 20 or 30 mg/kg i.p., 30 min after its administration. Pretreatment with calcitonin (2.5 UI/kg i.p.) 15 min before morphine (3 or 10 mg/kg i.p.) did not modify the effect of the opioid on plasma corticosterone. U-50,488H (0.5, 1, 5 or 15 mg/kg i.p.) induced an increase in the release of corticosterone only at the higher dose, 30 min after injection. Significantly higher plasma corticosterone levels after U-50,488H administration at doses of 0.5, 1 or 5 mg/kg i.p. were observed when calcitonin was administered 15 min before the kappa-opioid receptor agonist. The enhanced responsiveness of the hypothalamus-pituitary-adrenocortical axis to U-50,488H (1 mg/kg i.p.) in animals pretreated with calcitonin, was completely blocked by the selective kappa-opioid receptor antagonist, nor-binaltorphimine, suggesting a role of kappa-opioid receptors in mediating the calcitonin-induced supersensitivity to U-50,488H.(ABSTRACT TRUNCATED AT 250 WORDS)