The use of the plasma concentration-effect relationship as a tool for the study of the mechanism of action of naloxone effects on mood and endocrine function

The relationship between naloxone-plasma concentrations and their effects on mood and endocrine function was studied. Ten healthy volunteers received 1.0 mg/kg i.v. naloxone or placebo following a randomized double-blind design. Effects on mood, determined by a visual analogue scale and luteinizing hormone (LH) and naloxone-plasma concentrations were measured at selected times. Naloxone induced significant effects on confusion, bewilderment and indifference, and an increment in LH levels. The timecourse of the responses on confusion and bewilderment was similar to that of naloxone-plasma concentration, suggesting that these effects are directly related to the action of naloxone on its receptors. Responses for indifference and LH, however, exhibited a delayed onset. This delay could be due to an indirect action, i.e. to the participation of additional physiological mechanisms in a cascade-libe manner. The results show that analysis of the concentration-effect relationship can be a useful tool for understanding naloxone effects on mood and endocrine function.