Adrenal steroid hormones and ethanol self-administration in male rhesus macaques

Research output: Contribution to journalArticle

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Abstract

RATIONALE: Hypothalamic-pituitary-adrenal (HPA) axis hormones have neuroactive metabolites with receptor activity similar to ethanol.

OBJECTIVES: The present study related HPA hormones in naïve monkeys to ethanol self-administration.

METHODS: Morning plasma adrenocorticotropic hormone (ACTH), cortisol, deoxycorticosterone (DOC), aldosterone, and dehydroepiandrosterone-sulfate (DHEA-S) were measured longitudinally in male rhesus macaques (Macaca mulatta) induced to drink ethanol followed by access to ethanol (4 % w/v, in water) and water 22 h/day for 12 months.

RESULTS: During ethanol access, DOC increased among non-heavy (average intake over 12 months ≤3.0 g/kg/day, n = 23) but not among heavy drinkers (>3.0 g/kg/day, n = 9); aldosterone was greater among heavy drinkers after 6 months. The ratio of DOC/aldosterone decreased only among heavy drinkers after 6 or12 months of ethanol self-administration. ACTH only correlated significantly with DHEA-S, the ratio of cortisol/DHEA-S and DOC after the onset of ethanol access, the former two just in heavy drinkers. Baseline hormones did not predict subsequent ethanol intake over 12 months, but baseline DOC correlated with average blood-ethanol concentrations (BECs), among all monkeys and heavy drinkers as a group. During ethanol access, aldosterone and DOC correlated and tended to correlate, respectively, with 12-month average ethanol intake.

CONCLUSIONS: Ethanol self-administration lowered ACTH and selectively altered its adrenocortical regulation. Mineralocorticoids may compensate for adrenocortical adaptation among heavy drinkers and balance fluid homeostasis. As DOC was uniquely predictive of future BEC and not water intake, to the exclusion of aldosterone, GABAergic neuroactive metabolites of DOC may be risk factors for binge drinking to intoxication.

Original languageEnglish (US)
Pages (from-to)3425-3436
Number of pages12
JournalPsychopharmacology
Volume231
Issue number17
DOIs
StatePublished - Sep 1 2014

Fingerprint

Self Administration
Macaca mulatta
Ethanol
Desoxycorticosterone
Steroids
Hormones
Aldosterone
Dehydroepiandrosterone Sulfate
Adrenocorticotropic Hormone
Haplorhini
Binge Drinking
Mineralocorticoids
Water-Electrolyte Balance
Pituitary Hormones
Water
Drinking
Hydrocortisone
Homeostasis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Adrenal steroid hormones and ethanol self-administration in male rhesus macaques. / Helms, Christa; Park, Byung; Grant, Kathleen (Kathy).

In: Psychopharmacology, Vol. 231, No. 17, 01.09.2014, p. 3425-3436.

Research output: Contribution to journalArticle

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abstract = "RATIONALE: Hypothalamic-pituitary-adrenal (HPA) axis hormones have neuroactive metabolites with receptor activity similar to ethanol.OBJECTIVES: The present study related HPA hormones in na{\"i}ve monkeys to ethanol self-administration.METHODS: Morning plasma adrenocorticotropic hormone (ACTH), cortisol, deoxycorticosterone (DOC), aldosterone, and dehydroepiandrosterone-sulfate (DHEA-S) were measured longitudinally in male rhesus macaques (Macaca mulatta) induced to drink ethanol followed by access to ethanol (4 {\%} w/v, in water) and water 22 h/day for 12 months.RESULTS: During ethanol access, DOC increased among non-heavy (average intake over 12 months ≤3.0 g/kg/day, n = 23) but not among heavy drinkers (>3.0 g/kg/day, n = 9); aldosterone was greater among heavy drinkers after 6 months. The ratio of DOC/aldosterone decreased only among heavy drinkers after 6 or12 months of ethanol self-administration. ACTH only correlated significantly with DHEA-S, the ratio of cortisol/DHEA-S and DOC after the onset of ethanol access, the former two just in heavy drinkers. Baseline hormones did not predict subsequent ethanol intake over 12 months, but baseline DOC correlated with average blood-ethanol concentrations (BECs), among all monkeys and heavy drinkers as a group. During ethanol access, aldosterone and DOC correlated and tended to correlate, respectively, with 12-month average ethanol intake.CONCLUSIONS: Ethanol self-administration lowered ACTH and selectively altered its adrenocortical regulation. Mineralocorticoids may compensate for adrenocortical adaptation among heavy drinkers and balance fluid homeostasis. As DOC was uniquely predictive of future BEC and not water intake, to the exclusion of aldosterone, GABAergic neuroactive metabolites of DOC may be risk factors for binge drinking to intoxication.",
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N2 - RATIONALE: Hypothalamic-pituitary-adrenal (HPA) axis hormones have neuroactive metabolites with receptor activity similar to ethanol.OBJECTIVES: The present study related HPA hormones in naïve monkeys to ethanol self-administration.METHODS: Morning plasma adrenocorticotropic hormone (ACTH), cortisol, deoxycorticosterone (DOC), aldosterone, and dehydroepiandrosterone-sulfate (DHEA-S) were measured longitudinally in male rhesus macaques (Macaca mulatta) induced to drink ethanol followed by access to ethanol (4 % w/v, in water) and water 22 h/day for 12 months.RESULTS: During ethanol access, DOC increased among non-heavy (average intake over 12 months ≤3.0 g/kg/day, n = 23) but not among heavy drinkers (>3.0 g/kg/day, n = 9); aldosterone was greater among heavy drinkers after 6 months. The ratio of DOC/aldosterone decreased only among heavy drinkers after 6 or12 months of ethanol self-administration. ACTH only correlated significantly with DHEA-S, the ratio of cortisol/DHEA-S and DOC after the onset of ethanol access, the former two just in heavy drinkers. Baseline hormones did not predict subsequent ethanol intake over 12 months, but baseline DOC correlated with average blood-ethanol concentrations (BECs), among all monkeys and heavy drinkers as a group. During ethanol access, aldosterone and DOC correlated and tended to correlate, respectively, with 12-month average ethanol intake.CONCLUSIONS: Ethanol self-administration lowered ACTH and selectively altered its adrenocortical regulation. Mineralocorticoids may compensate for adrenocortical adaptation among heavy drinkers and balance fluid homeostasis. As DOC was uniquely predictive of future BEC and not water intake, to the exclusion of aldosterone, GABAergic neuroactive metabolites of DOC may be risk factors for binge drinking to intoxication.

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