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

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

International Journal of Neuropsychopharmacology 7(1): 71-75

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 Lis 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 Lis mood stabilization.

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Accession: 011859513

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PMID: 14725722

DOI: 10.1017/S1461145703003821

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