Endocrine Effects of Naloxone-Induced Opiate Receptor Blockade *

To test the effect of opiate receptor blockade on hormone release in man, we administered 10 mg naloxone iv to eight normal subjects and compared the results with those found after saline infusion. Naloxone produced a rise in serum cortisol (P < 0.01), LH (P < 0.01), FSH (P < 0.05), and insulin (P < 0.05) levels but did not alter serum GH, PRL, TSH, arginine vasopressin, glucagon, T3, or T4. Naloxon e had no effect on GH levels in two subjects with active acromegaly or on TSH levels i n six subjects with primary hypothyroidism. In dynamic pituitary function testing, naloxone diminished the GH response to arginine (P < 0.05) without altering the PRL response; naloxone augmented the PRL response to TRH (P < 0.025) without affecting the TSH response. Naloxone did not significantly alter GH or PRL response to L-dopa. Naloxone enhanced the increment in serum cortisol induced by the stress of gastroscopy without changing the GH or PRL response. Naloxone increased glucose response areas (P < 0.05) after an iv glucose bolus and raised the maximum plasma glucose level (P < 0.05) without altering the rate of glucose disappearance. Glucagon and insulin responses to glucose and arginine were not altered by naloxone. Psychological testing showed that naloxone altered performance on the Graham-Kendall Memory for Designs test in half of the subjects studied. There were no significant differences between saline and naloxone trials on the Profile of Mood States questionnaire or the mood-anxiety scale. Together with subjective reports from two of the subjects that naloxone decreased their ability to concentrate, these data suggest that opiate receptors may play a role in short term memory. Specific opiate receptor blockade with naloxone has definite endocrine and metabolic effects, suggesting endogenous opioid modulation of secretion of some of these hormones. Since these effects of naloxone are not always complementary to those of opiates, exogenous opiates may also act on separate receptors which are not blocked by naloxone.