These authors equally contributed to this study.
Chronic olanzapine treatment decreases arachidonic acid turnover and prostaglandin E2 concentration in rat brain
Article first published online: 20 SEP 2011
Published 2011. This article is a US Government work and is in the public domain in the USA
Journal of Neurochemistry
Volume 119, Issue 2, pages 364–376, October 2011
How to Cite
Cheon, Y., Park, J.-Y., Modi, H. R., Kim, H.-W., Lee, H.-J., Chang, L., Rao, J. S. and Rapoport, S. I. (2011), Chronic olanzapine treatment decreases arachidonic acid turnover and prostaglandin E2 concentration in rat brain. Journal of Neurochemistry, 119: 364–376. doi: 10.1111/j.1471-4159.2011.07410.x
- Issue published online: 5 OCT 2011
- Article first published online: 20 SEP 2011
- Accepted manuscript online: 4 AUG 2011 05:54AM EST
- Received April 5, 2011; revised manuscript received July 25, 2011; accepted August 1, 2011.
- bipolar disorder;
- prostaglandin E2;
J. Neurochem. (2011) 119, 364–376.
The atypical antipsychotic, olanzapine (OLZ), is used to treat bipolar disorder, but its therapeutic mechanism of action is not clear. Arachidonic acid (AA, 20:4n-6) plays a critical role in brain signaling and an up-regulated AA metabolic cascade was reported in postmortem brains from bipolar disorder patients. In this study, we tested whether, similar to the action of the mood stabilizers lithium, carbamazepine and valproate, chronic OLZ treatment would reduce AA turnover in rat brain. We administered OLZ (6 mg/kg/day) or vehicle i.p. to male rats once daily for 21 days. A washout group received 21 days of OLZ followed by vehicle on day 22. Two hours after the last injection, [1-14C]AA was infused intravenously for 5 min, and timed arterial blood samples were taken. After the rat was killed at 5 min, its brain was microwaved, removed and analyzed. Chronic OLZ decreased plasma unesterified AA concentration, AA incorporation rates and AA turnover in brain phospholipids. These effects were absent after washout. Consistent with reduced AA turnover, OLZ decreased brain cyclooxygenase activity and the brain concentration of the proinflammatory AA-derived metabolite, prostaglandin E2, In view of up-regulated brain AA metabolic markers in bipolar disorder, the abilities of OLZ and the mood stabilizers to commonly decrease prostaglandin E2, and AA turnover in rat brain phospholipids, albeit by different mechanisms, may be related to their efficacy against the disease.