The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 1 64-68
Copyright © 1999 by The Endocrine Society
From the Clinical Research Centers |
Adrenocorticotropin Responses to Naloxone in Sons of Alcohol-Dependent Men1
Gary S. Wand,
Deborah Mangold and
Mahmood Ali
Departments of Medicine and Psychiatry, The Johns Hopkins
University School of Medicine, Baltimore, Maryland 21205
Address all correspondence and requests for reprints to: Gary S. Wand, M.D., The Johns Hopkins University School of Medicine, Ross Research Building, Room 850, 720 Rutland Avenue, Baltimore, Maryland 21205. E-mail: gwand{at}welchlink.welch.jhu.edu
The endogenous opioid system is part of a neural circuitry functionally
related to alcohol-seeking behaviors. A family history of alcoholism 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 corticotropin-releasing
factor neurons, thereby providing a methodology for comparing
hypothalamic opioid tone between study groups. Sixty nonalcoholic
subjects, aged 1825 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 naloxone (125 µg/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.
Copyright © 1999 by The Endocrine Society