Adrenocorticotropin and cortisol responses to a naloxone challenge and risk of alcoholism.
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 microg/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.
Hernandez-Avila
Carlos A
CA
Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-2103, USA.
Oncken
Cheryl
C
Van Kirk
Jeffrey
J
Wand
Gary
G
Kranzler
Henry R
HR
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology; D000704:Analysis of Variance; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007262:Infusions, Intravenous; D008297:Male; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage
D009292:Narcotic Antagonists; D009270:Naloxone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone