The effect of naloxone on adrenocorticotropin and cortisol release: evidence for a reduced response in depression

Background. Endogenous opioid peptides inhibit the hypothalamic-pituitary-adrenal (HPA) axis by influencing the release of hypothalamic corticotropin releasing factors. This study examines whether increased activity of the HPA axis in major depression is associated with reduced opioid tone. Methods. We measured the adrenocorticotropin (ACTH) and cortisol responses to an intravenous bolus of naloxone 0.125 mu g/kg in 13 depressed outpatients and 13 healthy volunteers. Results. The mean cortisol response was significantly reduced (P < 0.05), and the ACTH response was also non significantly reduced in the depressed subjects. Conclusions. These findings imply that the degree of inhibitory endogenous opioid tone is reduced in depression. Various mechanisms for the finding are discussed, including possible alteration in the function of alpha-adrenergic pathways. Clinical implications. Reduced endogenous opioid tone may explain why some depressed individuals self-medicate with opiates, and depression is associated with opiate withdrawal. Opioid pathways may have a role in the mechanism of action of antidepressant drugs, and may be of relevance in the development of novel antidepressants. Limitations of the study. The sample size was small, leading to a failure of the difference of the basal cortisol levels and also the delta ACTH between the groups to reach statistical significance. (C) 1999 Elsevier Science B.V. All rights reserved.