Effects of intracerebroventricular clonidine on the hypothalamic noradrenaline and plasma corticosterone levels of opiate naive rats and after naloxone-induced withdrawal

Abstract

The aim of this study was to determine whether hypothalamic noradrenergic neuronal activity contributes to the abstinence-induced hypersecretion of corticosterone during naloxone-induced withdrawal. With this purpose the effects of intracerebroventricular (i.c.v.) clonidine on hypothalamic noradrenaline (NA) and plasma corticosterone were studied in chronically placebo-treated rats (controls) and during naloxone-induced morphine withdrawal. In control rats, clonidine (10 μg) significantly increased plasma levels of corticosterone without changing the hypothalamic content of NA. Naloxone (1 mg/kg, s.c.) also increased plasma corticosterone levels and clonidine administered prior to naloxone, antagonized the effect of naloxone on plasma corticosterone. In chronically morphine-treated rats, naloxone treatment induced an increase in plasma corticosterone and reduced the hypothalamic NA content. Clonidine significantly prevented the reduction in the hypothalamic NA, without modifying plasma levels of corticosterone. The results show an interaction between opioid-receptors and α 2-adrenoceptors in the hypothalamus, and suggest that mechanisms other than hyperactivity of NA neurons contribute to the hypothalamus-pituitary-adrenocortical (HPA) axis hyperactivity during the opiate withdrawal.