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Gary S. Wand, MD; Deborah Mangold, MA; Samer El Deiry, MD, PhD; Mary E. McCaul, PhD; Donald Hoover, PhD

Arch Gen Psychiatry. 1998;55:1114-1119.

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 µg/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-µg/kg dose of naloxone hydrochloride with no further increase in cortisol levels observed following the 375-µg/kg dose. Family history–negative subjects had a diminished cortisol response to the 125-µg/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.

From The Johns Hopkins University School of Medicine (Drs Wand, El Deiry, and McCaul and Ms Mangold) and The Johns Hopkins University School of Public Health (Dr Hoover), Baltimore, Md.

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