SEROTONERGIC MECHANISMS INVOLVED IN CALCITONIN POTENTIATION OF KAPPA-OPIOID RECEPTOR-MEDIATED EFFECTS ON ADRENAL SECRETION

Calcitonin can selectively modulate the effects of opioids on the rat hypothalamic-pituitary-adrenal axis and increase the release of cortic osterone induced by a K-opioid receptor agonist. Considerable evidence supports the involvement of opioid and serotonergic systems in the an algesic effect of calcitonin. In this study, the involvement of hypoth alamic serotonergic pathways in the calcitonin potentiation of the eff ect of -(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]- benzeneacetamide methane sulphonate (U-50,488H) on the secretion of co rticosterone was examined. The correlation between the calcitonin-indu ced potentiation of the pituitary-adrenal response to U-50,488H and ch anges in serotonin turnover was evaluated. Our results show that the i ncrease in the release of corticosterone induced by treatment with cal citonin + U-50,488H was not evident when the turnover of serotonin was decreased by inhibition of its synthesis with m-hydroxybenzylhydrazin e (NSD 1015) or by blockade of its metabolism with trans-2-phenylcyclo propylamine (tranylcypromine). Although other factors can not be disca rded, from the present data it can be suggested that the serotonergic system plays an important role in the interaction calcitonin-kappa-opi oid receptor agonist in the hypothalamic-pituitary-adrenal axis. (C) 1 997 Elsevier Science B.V.