Chronic lithium treatment affects rat brain and serum dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) levels

Rachel Maayan, Galit Shaltiel, Michael Poyurovsky, Edward Ramadan, Oren Morad, Allon Nechmad, Abraham Weizman, Galila Agam

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Lithium (Li) is an established effective treatment for bipolar disorder. However, the molecular mechanism of its action is still unknown. Dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S) are adrenal hormones also synthesized de novo in the brain as neurosteroids. Recent studies have suggested that DHEA has mood-elevating properties and may demonstrate antidepressant effects. 3′(2′)-Phosphoadenosine 5′-phosphate (PAP) phosphatase is a novel Li-inhibitable enzyme involved in sulphation processes. In the present study we examined the impact of 10 d Li treatment on serum and brain DHEA and DHEA-S levels in rats. Our results show that Li administration lowered frontal cortex and hippocampus DHEA and DHEA-S levels, in line with our hypothesis assuming that Li's inhibition of PAP phosphatase leads to elevated PAP levels resulting in inhibition of sulphation and reduction in brain DHEA-S levels. Future studies should address the involvement of neurosteroids in the mechanism of Li's mood stabilization.

Original languageEnglish
Pages (from-to)71-75
Number of pages5
JournalInternational Journal of Neuropsychopharmacology
Volume7
Issue number1
DOIs
StatePublished - 1 Mar 2004

Keywords

  • 3′(2′)-phosphoadenosine 5′-phosphate phosphatase
  • Brain
  • Dehydroepiandrosterone
  • Dehydroepiandrosterone-sulphate
  • Lithium
  • Serum

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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