Adrenocorticotropin Responses to Naloxone in Sons of Alcohol-Dependent Men

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Abstract
The endogenous opioid system is part of a neural circuitry func- tionally related to alcohol-seeking behaviors. A family history of al- coholism is the strongest predictor of future development of alcohol dependence. This study was designed to evaluate ACTH responses to opioid receptor blockade as a function of family history for alcohol dependence. The nonselective opioid antagonist naloxone stimulates ACTH secretion by blocking opioidergic input on paraventricular cor- ticotropin-releasing factor neurons, thereby providing a methodology for comparing hypothalamic opioid tone between study groups. Sixty nonalcoholic subjects, aged 18 -25 yr, were enrolled in a protocol to measure the ACTH response to naloxone. Thirty-two subjects were offspring from families with a high density of alcohol dependence and were designated as family history-positive subjects. Twenty-eight subjects were offspring of nonalcohol-dependent parents and were designated family history-negative subjects. Subjects received nal- oxone (125 mg/kg) or placebo (0.9% saline) in double blind, randomized order. Plasma ACTH was monitored. Family history-positive men had increased ACTH response to naloxone compared to 1) family history- positive women, 2) family history-negative men, and 3) family history- negative women. Despite differences in plasma ACTH levels after naloxone administration, plasma naloxone concentrations did not differ between study groups. This finding suggests that nonalcoholic male offspring of alcohol-dependent men have altered endogenous opioid activity directed at hypothalamic corticotropin-releasing factor neurons. (J Clin Endocrinol Metab 84: 64 - 68, 1999)

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