Effects of clonidine on pituitary-adrenocortical axis in morphine-tolerant rats and after naloxone-induced withdrawal.

The effects of systemically administered clonidine on pituitary-adrenocortical axis in morphine-tolerant rats and after naloxone-induced withdrawal were examined. In naive animals, clonidine (0.5 and 1 mg/kg s.c.) significantly increased plasma beta-endorphin-like immunoreactivity (beta-END-LI) and cortisol levels. This effect was significantly reduced in morphine-tolerant animals. Naloxone treatment induced an increase of plasma beta-END-LI and cortisol levels in morphine-tolerant animals. The increase in cortisol level after withdrawal was significantly reduced by clonidine. These results are consistent with an interaction between alpha 2-adrenoceptors and opioid systems in the control of pituitary-adrenocortical axis during morphine tolerance and withdrawal.