Plasma β-endorphin and cortisol levels in morphine-tolerant rats and in naloxone-induced withdrawal

The relationship between morphine tolerance and pituitary-adrenocortical activity was examined. In rats made tolerant to morphine by implantation of morphine-containing pellets, there was a significant reduction in plasma levels of β-endorphin-like immunoreactivity (β-END-LI), whereas no significant changes in cortisol levels were seen. Naloxone treatment induced an increase in plasma β-END-LI and cortisol levels in morphine-tolerant animals. Additionally, acute morphine administration induced an increase in plasma levels of β-END-LI and cortisol, an effect which was prevented by naloxone. These results are consistent with an increased release of pro-opiomelanocortin-derived peptides after acute morphine and with a decreased release of these peptides in tolerant rats, and suggest that opioid peptides play an important role in the regulation of pituitary-adrenocortical function.