Family history of alcoholism and hypothalamic opioidergic activity.
BACKGROUND
This study was designed to assess whether nonalcoholic offspring from families with a high density of alcohol-dependent individuals have altered endogenous central nervous system opioid activity. Naloxone hydrochloride stimulates plasma cortisol by blocking opioidergic input on the corticotropin-releasing factor neuron, thereby providing a noninvasive method for measuring hypothalamic opioid tone.


METHODS
Forty-eight nonalcoholic subjects aged 18 to 25 years were enrolled in a protocol to measure endogenous opioid activity by inducing opioid receptor blockade with the receptor antagonist, naloxone. Twenty-six subjects were offspring from families with a high density of alcohol dependence and were designated as family history-positive subjects. Twenty-two subjects were biological offspring of nonalcohol-dependent parents and designated as family history-negative subjects. Subjects received naloxone hydrochloride (0, 125, and 375 microg/kg) in double-blind, randomized order. Serum cortisol levels were monitored.


RESULTS
Family history-negative subjects had a graded cortisol response to each dose of naloxone. In contrast, family history-positive subjects achieved a maximal cortisol response to the 125-microg/kg dose of naloxone hydrochloride with no further increase in cortisol levels observed following the 375-microg/kg dose. Family history-negative subjects had a diminished cortisol response to the 125-microg/kg dose compared with the family history-positive subjects. Plasma naloxone concentrations did not differ between family history groups.


CONCLUSIONS
Individuals from families with a high density of alcohol dependence are more sensitive to naloxone compared with offspring of nonalcohol-dependent parents. This implies that individuals with a family history of alcohol dependence have diminished endogenous hypothalamic opioid activity.
Wand
G S
GS
The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. GWAND@WELCHLINK.WELCH.JHU.EDU
Mangold
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El Deiry
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McCaul
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Hoover
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D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005190:Family; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007031:Hypothalamus / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D008297:Male; D009270:Naloxone / Q000097:blood / Q000494:pharmacology; D018847:Opioid Peptides / Q000032:analysis* / Q000037:antagonists & inhibitors; D011957:Receptors, Opioid / Q000187:drug effects
D018847:Opioid Peptides; D011957:Receptors, Opioid; D009270:Naloxone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone