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Journal of Lipid Research, Vol. 47, 172-180, January 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats

James C. DeMar, Jr.^*, Kiazong Ma^*, Jane M. Bell^*, Miki Igarashi^*, Deanna Greenstein and Stanley I. Rapoport^1,*

^* Brain Physiology and Metabolism Section, National Institute on Aging, and Child Psychiatry Branch, National Institutes of Health Bethesda, MD, 20892
National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892

Published, JLR Papers in Press, October 6, 2005.

¹ To whom correspondence should be addressed. e-mail: sir{at}helix.nih.gov

Male rat pups at weaning (21 days of age) were subjected to a diet deficient or adequate in n-3 polyunsaturated fatty acids (n-3 PUFAs) for 15 weeks. Performance on tests of locomotor activity, depression, and aggression was measured in that order during the ensuing 3 weeks, after which brain lipid composition was determined. In the n-3 PUFA-deprived rats, compared with n-3 PUFA-adequate rats, docosahexaenoic acid (22:6n-3) in brain phospholipid was reduced by 36% and docosapentaenoic acid (22:5n-6) was elevated by 90%, whereas brain phospholipid concentrations were unchanged. N-3 PUFA-deprived rats had a significantly increased (P = 0.03) score on the Porsolt forced-swim test for depression, and increased blocking time (P = 0.03) and blocking number (P = 0.04) scores (uncorrected for multiple comparisons) on the isolation-induced resident-intruder test for aggression. Large effect sizes (d > 0.8) were found on the depression score and on the blocking time score of the aggression test. Scores on the open-field test for locomotor activity did not differ significantly between groups, and had only small to medium effect sizes. This single-generational n-3 PUFA-deprived rat model, which demonstrated significant changes in brain lipid composition and in test scores for depression and aggression, may be useful for elucidating the contribution of disturbed brain PUFA metabolism to human depression, aggression, and bipolar disorder.

Supplementary key words docosahexaenoic • locomotor • rat • activity • behavior • diet

Abbreviations: ARA, arachidonic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; FAME, fatty acid methyl ester; LA, linoleic acid; -LNA, -linolenic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; PS, phosphatidylserine; PUFA, polyunsaturated fatty acid; SSRI, selective serotonin reuptake inhibitor; TLC, thin-layer chromatography

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