Hypothalamic-pituitary-adrenal axis and ethanol modulation of deoxycorticosterone levels in cynomolgus monkeys

Patrizia Porcu, Kathleen (Kathy) Grant, Heather L. Green, Laura S M Rogers, A. Leslie Morrow

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Rationale: The metabolites of deoxycorticosterone (DOC) and progesterone, allotetrahydrodeoxycorticosterone and allopregnanolone, are potent endogenous neuroactive steroids that are increased in rodent brain and plasma after hypothalamic-pituitary-adrenal (HPA) axis activation by acute stress or ethanol administration. However, little data are available for male nonhuman primates. Objective: To determine DOC concentrations in plasma samples from 11 monkeys following challenge of the HPA axis with naloxone, corticotropin-releasing factor (CRF), dexamethasone, adrenocorticotropic hormone (ACTH) following dexamethasone pretreatment and ethanol. Methods: DOC levels were measured in monkey plasma by radioimmunoassay. Results: DOC levels were increased after naloxone (125 μg/kg and 375 μg/kg, respectively) and CRF administration (1 μg/kg), and decreased following dexamethasone (130 μg/kg) administration. ACTH (10 ng/kg) challenge, 4-6 h after 0.5 mg/kg dexamethasone, and administration of ethanol (1.0 g/kg and 1.5 g/kg) had no effect on DOC concentrations. DOC levels were positively correlated with cortisol and ACTH levels after the naloxone (375 μg/kg), CRF, and ACTH challenges. Finally, the suppression of DOC levels measured after dexamethasone was negatively correlated with subsequent alcohol self-administration. Conclusions: These results suggest that DOC levels in monkeys are regulated by the HPA axis and may contribute to physiological responses following activation.

Original languageEnglish (US)
Pages (from-to)293-301
Number of pages9
JournalPsychopharmacology
Volume186
Issue number3
DOIs
StatePublished - Jun 2006
Externally publishedYes

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Desoxycorticosterone
Macaca fascicularis
Ethanol
Dexamethasone
Corticotropin-Releasing Hormone
Adrenocorticotropic Hormone
Naloxone
Haplorhini
Pregnanolone
Self Administration
Primates
Radioimmunoassay
Progesterone
Hydrocortisone
Rodentia
Steroids
Alcohols
Brain

Keywords

  • Cynomolgus monkeys
  • Deoxycorticosterone (DOC)
  • Ethanol
  • Hypothalamic-pituitary-adrenal axis

ASJC Scopus subject areas

  • Pharmacology

Cite this

Hypothalamic-pituitary-adrenal axis and ethanol modulation of deoxycorticosterone levels in cynomolgus monkeys. / Porcu, Patrizia; Grant, Kathleen (Kathy); Green, Heather L.; Rogers, Laura S M; Morrow, A. Leslie.

In: Psychopharmacology, Vol. 186, No. 3, 06.2006, p. 293-301.

Research output: Contribution to journalArticle

Porcu, Patrizia ; Grant, Kathleen (Kathy) ; Green, Heather L. ; Rogers, Laura S M ; Morrow, A. Leslie. / Hypothalamic-pituitary-adrenal axis and ethanol modulation of deoxycorticosterone levels in cynomolgus monkeys. In: Psychopharmacology. 2006 ; Vol. 186, No. 3. pp. 293-301.
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