Family history of alcoholism and hypothalamic opioidergic activity

Background: This study was designed to assess whether nonalcoholic offsprin g from families with a high density of alcohol-dependent individuals have a ltered endogenous central nervous system opioid activity. Naloxone hydrochl oride stimulates plasma cortisol by blocking opioidergic input on the corti cotropin-releasing factor neuron, thereby providing a noninvasive method fo r measuring hypothalamic opioid tone. Methods: Forty-eight nonalcoholic subjects aged 18 to 25 years were enrolle d in a protocol to measure endogenous opioid activity by inducing opioid re ceptor 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 w ere biological offspring of nonalcohol-dependent parents and designated as family history-negative subjects. Subjects received naloxone hydrochloride (0, 125; and 375 mu g/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 achie ved a maximal cortisol response to the 125-mu g/kg dose of nalaxone hydroch loride with no further increase in cortisol levels observed following the 3 75-mu g/kg dose. Family history-negative subjects had a diminished cortisol response to the 125-mu g/kg dose compared with the family history-positive subjects. Plasma naloxone concentrations did not differ between family his tory groups. Conclusions: Individuals from families with a high density of alcohol depen dence are more sensitive to naloxone compared with offspring of nonalcohol- dependent parents. This implies that individuals with a family history of a lcohol dependence have diminished endogenous hypothalamic opioid activity.