Chronic lithium treatment affects rat brain and serum dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) levels.
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.
Maayan
Rachel
R
Laboratory of Biological Psychiatry, Felsentein Medical Research Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Shaltiel
Galit
G
Poyurovsky
Michael
M
Ramadan
Edward
E
Morad
Oren
O
Nechmad
Allon
A
Weizman
Abraham
A
Agam
Galila
G
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D008094:Lithium