Adrenocorticotropin responses to naloxone in sons of alcohol-dependent men

The endogenous opioid system is part of a neural circuitry functionally rel ated to alcohol-seeking behaviors. A family history of alcoholism is the st rongest predictor of future development of alcohol dependence. This study w as designed to,evaluate ACTH responses to opioid receptor blockade as a fun ction of family history for alcohol dependence. The nonselective opioid ant agonist naloxone stimulates ACTH secretion by blocking opioidergic input on paraventricular corticotropin-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 f rom families with a high density of alcohol dependence and mere designated as family history-positive subjects. Twenty-eight subjects mere offspring o f nonalcohol-dependent parents and were designated family history-negative subjects. Subjects received naloxone (125 mu g/kg) or placebo (0.9% saline) in double blind, randomized order. Plasma ACTH was monitored. Family histo ry-positive men had increased ACTH response to naloxone compared to 1) fami ly history-positive women, 2) family history-negative men, and 3) family hi story-negative women. Despite differences in plasma ACTH levels after nalox one administration, plasma naloxone concentrations did not differ between s tudy groups. This finding suggests that nonalcoholic male offspring of alco hol-dependent men have altered endogenous opioid activity directed at hypot halamic corticotropin-releasing factor neurons.