L-type Ca 2+ channel ligands modulate morphine effects on the hypothalamus-pituitary-adrenocortical axis in rats

Abstract

The role of the L-type Ca 2+ channel in the acute effects of morphine on the hypothalamo-pituitary-adrenocortical (HPA) system was studied by administration of the Ca 2+ channel agonist, BAY K 8644, and the antagonists, verapamil and nimodipine, to rats. Morphine (30 mg/kg i.p.) induced an increase in corticosterone secretion 30 min after injection, which was correlated with a simultaneous change in hypothalamic noradrenaline (NA) and dopamine DA) contents. Pretreatment with verapamil (10 or 20 mg/kg i.p.) or nimodipine (5 mg/kg i.p.) antagonized the HPA activation induced by morphine, blocking both the decrease in hypothalamic NA levels and the elevation in plasma corticosterone induced by the opioid. BAY K 8644 (2 mg/kg i.p.) potentiated the effects of morphine, decreasing the hypothalamic NA content and increasing the release of corticosterone. The Ca 2+ channel antagonist, nimodipine, given alone induced a slight reduction in hypothalamic NA content but did not modify plasma corticosterone levels. Verapamil given alone did not alter HPA activity. Instead, the Ca 2+ agonist decreased the hypothalamic catecholamine content and increased plasma corticosterone levels. These results indicate that Ca 2+ influx is necessary for the expression of opioid actions on the HPA system, and suggest that the Ca 2+ flux in hypothalamic neurons is functionally linked to activation of opioid receptors.