Opioidergic inhibition of circulatory and endocrine stress responses in cynomolgus monkeys: a preliminary study.

Twenty-five female cynomolgus monkeys (Macaca fascicularis) were exposed to psychological stress (threat of capture) after blockade of endogenous opioids with naloxone and after saline control injections. Heart rates were monitored continuously and blood samples were obtained for determination of plasma levels of cortisol and beta-endorphin-like immunoreactivity. Results indicate that the stress manipulation resulted in increased heart rates as well as plasma cortisol levels in monkeys pretreated with saline. Blockade of opioid receptors with naloxone potentiated the stress-induced rise in plasma cortisol and stimulated release of beta-endorphin-like immunoreactivity. The drug effect on heart rate reactivity was significantly correlated with the drug effects on both cortisol and beta-endorphin. When saline-treated monkeys were divided into high and low heart rate reactivity groups, the effects of naloxone on heart rate, cortisol, and beta-endorphin-like immunoreactivity responsiveness were significantly greater in low heart rate reactors. These data suggest that monkeys with low heart rate responses to stress have an effective opioidergic inhibition of circulatory and pituitary-adrenocortical reactivity. Monkeys showing excessive heart rate reactivity during psychological stress have a less active opioidergic inhibitory mechanism. The potential pathophysiological consequences of impaired opioidergic inhibition are discussed in light of the relationship between exaggerated stress reactivity and atherosclerotic lesion formation.