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Journal of Lipid Research, Vol. 49, 162-168, January 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Chronic N-methyl-D-aspartate administration increases the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat

Ho-Joo Lee^*, Jagadeesh S. Rao^*, Lisa Chang^*, Stanley I. Rapoport^* and Richard P. Bazinet^1,*,

^* Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Published, JLR Papers in Press, October 23, 2007.

¹ To whom correspondence should be addressed. e-mail: richard.bazinet{at}utoronto.ca

Whereas antibipolar drug administration to rats reduces brain arachidonic acid turnover, excessive N-methyl-D-aspartate (NMDA) signaling is thought to contribute to bipolar disorder symptoms and may increase arachidonic acid turnover in rat brain phospholipids. To determine whether chronic NMDA would increase brain arachidonic acid turnover, rats were daily administered NMDA (25 mg/kg, ip) or vehicle for 21 days. In unanesthetized rats, on day 21, [1-¹⁴C]arachidonic acid was infused intravenously and arterial blood plasma was sampled until the animal was euthanized at 5 min and its microwaved brain was subjected to chemical and radiotracer analysis. Using equations from our in vivo fatty acid model, we found that compared with controls, chronic NMDA increased the net rate of incorporation of plasma unesterified arachidonic acid into brain phospholipids (25–34%) as well as the turnover of arachidonic acid within brain phospholipids (35–58%). These changes were absent at 3 h after a single NMDA injection. The changes, opposite to those after chronic administration of antimanic drugs to rats, suggest that excessive NMDA signaling via arachidonic acid may be a model of upregulated arachidonic acid turnover in brain phospholipids.

Supplementary key words bipolar disorder • signaling • neuroreceptor

Abbreviations: ChoGpl, choline glycerophospholipid; cPLA₂, calcium-dependent cytosolic phospholipase A₂; EtnGpl, ethanolamine glycerophospholipid; NMDA, N-methyl-D-aspartate; PtdIns, phosphatidylinositol; PtdSer, phosphatidylserine

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