Journal
MOLECULAR PSYCHIATRY
Volume 7, Issue 8, Pages 845-850Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.mp.4001111
Keywords
lithium; arachidonic acid; cyclooxygenase; phospholipase A(2); prostaglandin; brain; rat; chronic; bipolar disorder
Funding
- NATIONAL INSTITUTE ON AGING [ZIAAG000145, Z01AG000145] Funding Source: NIH RePORTER
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Rats treated with lithium chloride for 6 weeks have been reported to demonstrate reduced turnover of arachidonic acid (AA) in brain phospholipids, and decreases in mRNA and protein levels, and enzyme activity, of AA-selective cytosolic phospholipase A(2) (cPLA(2)). We now report that chronic lithium administration to rats significantly reduced the brain protein level and enzyme activity of cyclooxygenase-2 (COX-2), without affecting COX-2 mRNA. Lithium also reduced the brain concentration of prostaglandin E-2 (PGE(2)), a bioactive product of AA formed via the COX reaction. COX-1 and the Ca2+ independent iPLA(2) (type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA(2) and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.
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