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Arch Gen Psychiatry. 1998 Dec;55(12):1114-9.

Family history of alcoholism and hypothalamic opioidergic activity.

Author information

  • 1The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. GWAND@WELCHLINK.WELCH.JHU.EDU

Abstract

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.

PMID:
9862555
[PubMed - indexed for MEDLINE]
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