Adrenocorticotropin and cortisol responses to a naloxone challenge and risk of alcoholism

Carlos A. Hernandez-Avila, Cheryl Oncken, Jeffrey Van Kirk, Gary Wand, Henry R. Kranzler

Research output: Contribution to journalArticlepeer-review


Background: Because abnormalities in opioid neurotransmission appear to underlie some of the inherited risk for alcoholism, we examined the effects of naloxone, an opioid antagonist, on corticotropin and cortisol responses in nonalcoholic subjects differentiated by paternal history of alcoholism. Methods: Placebo-controlled, balanced, within-subject design involving 2 test days over a period of 3 to 7 days. Thirty-six subjects (67% male; 53% paternal-history-positive; mean age = 25.0 years) were screened to exclude substance abuse or dependence. Subjects received intravenous naloxone 125 μg/kg or placebo, with sessions in random order. Plasma corticotropin and cortisol were measured for up to 120 min post infusion. Results: Corticotropin responses at baseline and following naloxone did not differ by paternal history of alcoholism; however, paternal-history-positive subjects exhibited greater cortisol concentrations at baseline, and at 15 and 30 min after naloxone administration. Paternal-history-positive subjects also had an earlier and greater peak cortisol response to naloxone and a nonsignificant trend for a greater area under the cortisol time curve than paternal-history-negative subjects. Conclusions: These findings suggest that individuals with greater vulnerability to alcoholism may have altered Hypothalamic-pituitary axis (HPA) dynamics, a finding that is consistent with a growing body of data on the role of opioidergic neurotransmission in the inherited risk of alcoholism.

Original languageEnglish (US)
Pages (from-to)652-658
Number of pages7
JournalBiological psychiatry
Issue number8
StatePublished - Apr 15 2002


  • ACTH
  • Alcohol dependence
  • Alcoholism
  • Cortisol
  • HPA axis
  • Naloxone

ASJC Scopus subject areas

  • Biological Psychiatry

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