Opioid regulation of hypothalamic-pituitary-adrenal function in depression

A morphine infusion paradigm was used to investigate opioid mechanisms in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression. The subjects were unmedicated psychiatric inpatients and healthy volunteers. Morphine suppressed cortisol secretion. Early resumption of cortisol secretion was associated with a diagnosis of major depression and abnormal dexamethasone suppression test results. Our data suggest that the hyperactivity of the HPA axis observed in depression is abnormally resistant to opioid inhibition as well as glucocorticoid feedback.