title: Developmental effects of dietary n-3 fatty acids on activity and response to novelty.
abstract: Insufficient availability of n-3 polyunsaturated fatty acids (PUFA) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n-3) in the developing brain. Low tissue levels of DHA are associated with neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD). In this study, 1st- and 2nd-litter male Long-Evans rats were raised from conception on a Control diet containing alpha-linolenic acid (4.20 g/kg diet), the dietarily essential fatty acid precursor of DHA, or a diet Deficient in alpha-linolenic acid (0.38 g/kg diet). The Deficient diet resulted in a decrease in brain phospholipid DHA of 48% in 1st-litter pups and 65% in 2nd-litter pups. Activity, habituation, and response to spatial change in a familiar environment were assessed in a single-session behavioral paradigm at postnatal days 28 and 70, inclusive. Activity and habituation varied by age with younger rats exhibiting higher activity, less habituation, and less stimulation of activity induced by spatial novelty. During the first and second exposures to the test chamber, 2nd-litter Deficient pups exhibited higher levels of activity than Control rats or 1st-litter Deficient pups, and less habituation during the first exposure, but were not more active after introduction of a novel spatial stimulus. The higher level of activity in a familiar environment, but not after introduction of a novel stimulus is consistent with clinical observations in ADHD. The observation of this effect only in 2nd-litter rats fed the Deficient diet suggests that brain DHA content, rather than dietary n-3 PUFA content, likely underlies these effects.
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA. blevant@kumc.edu
authors.forename: Beth
authors.initials: B
authors.lastname: Levant
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Zarcone
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Fowler
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism*; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology*; D006185:Habituation, Psychophysiologic / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D017962:alpha-Linolenic Acid / Q000172:deficiency / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids
references.citation: Nutr Neurosci. 2010 Aug;13(4):161-9
references.pmid: 20670471
references.citation: Clin Pediatr (Phila). 1987 Aug;26(8):406-11
references.pmid: 2439249
references.citation: Dev Psychobiol. 1983 Mar;16(2):83-109
references.pmid: 6339302
references.citation: Pediatrics. 1981 Jan;67(1):13-7
references.pmid: 7243422
references.citation: Am J Clin Nutr. 2002 Apr;75(4):662-7
references.pmid: 11916751
references.citation: Pharmacol Biochem Behav. 1999 Dec;64(4):821-6
references.pmid: 10593206
references.citation: Psychopharmacology (Berl). 1991;105(1):93-100
references.pmid: 1745717
references.citation: Lipids. 1991 Mar;26(3):203-8
references.pmid: 2046487
references.citation: J Neurosci Methods. 2001 May 30;107(1-2):107-24
references.pmid: 11389948
references.citation: Behav Brain Res. 1998 Jul;94(1):11-24
references.pmid: 9708835
references.citation: J Lipid Res. 2007 Nov;48(11):2471-7
references.pmid: 17703057
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):329-49
references.pmid: 16949263
references.citation: Physiol Behav. 1994 Feb;55(2):231-9
references.pmid: 8153160
references.citation: Ann N Y Acad Sci. 1969 Jul 30;159(3):1059-70
references.pmid: 5260289
references.citation: J Nutr. 1993 Nov;123(11):1939-51
references.pmid: 8229312
references.citation: Neurosci Lett. 1998 Jan 16;240(3):177-81
references.pmid: 9502233
references.citation: Psychoneuroendocrinology. 2008 Oct;33(9):1279-92
references.pmid: 18707812
references.citation: J Pharmacol Exp Ther. 1995 Oct;275(1):345-57
references.pmid: 7562570
references.citation: Neuropharmacology. 2009 Dec;57(7-8):636-9
references.pmid: 19715711
references.citation: J Nutr. 2007 Jan;137(1):125-9
references.pmid: 17182812
references.citation: Dev Neurosci. 2000 Sep-Dec;22(5-6):474-80
references.pmid: 11111165
references.citation: Eur J Pediatr. 2010 Feb;169(2):149-64
references.pmid: 19672626
references.citation: Neurosci Lett. 2000 Apr 21;284(1-2):25-8
references.pmid: 10771153
references.citation: Psychopharmacologia. 1972;24(1):99-106
references.pmid: 4622973
references.citation: Dev Med Child Neurol. 2009 Aug;51(8):580-92
references.pmid: 19549202
references.citation: Physiol Behav. 2006 Sep 30;89(2):196-204
references.pmid: 16875705
references.citation: J Neurochem. 1996 Apr;66(4):1582-91
references.pmid: 8627314
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):299-308
references.pmid: 16962757
references.citation: J Abnorm Child Psychol. 1989 Aug;17(4):371-91
references.pmid: 2794253
references.citation: Nutr J. 2008 Feb 14;7:8
references.pmid: 18275609
references.citation: J Lipid Res. 2000 Jan;41(1):32-40
references.pmid: 10627499
references.citation: J Neurosci Methods. 2010 May 30;189(1):36-43
references.pmid: 20346982
references.citation: Lipids. 2001 Sep;36(9):859-71
references.pmid: 11724458
references.citation: Am J Clin Nutr. 1995 Oct;62(4):761-8
references.pmid: 7572706
references.citation: Lipids. 2006 May;41(5):407-14
references.pmid: 16933785
references.citation: Biol Psychiatry. 2006 Nov 15;60(10):1053-61
references.pmid: 16893529
references.citation: Nutr Neurosci. 2003 Oct;6(5):277-81
references.pmid: 14609313
references.citation: J Neurochem. 2008 Jul;106(2):662-71
references.pmid: 18410511
references.citation: Behav Brain Res. 1998 Jul;94(1):1-10
references.pmid: 9708834
references.citation: Behav Brain Res. 2007 Jun 18;180(2):119-26
references.pmid: 17397943
references.citation: Neurosci Biobehav Rev. 2006;30(7):1045-64
references.pmid: 16774787
references.citation: J Am Acad Child Adolesc Psychiatry. 1996 Feb;35(2):204-14
references.pmid: 8720630
references.citation: Am J Clin Nutr. 2000 Jan;71(1 Suppl):327S-30S
references.pmid: 10617991
references.citation: J Nutr. 2006 Aug;136(8):2236-42
references.pmid: 16857847
references.citation: Behav Brain Res. 2004 Jun 4;152(1):49-57
references.pmid: 15135968
references.citation: J Nutr. 2007 Nov;137(11):2425-30
references.pmid: 17951480
references.citation: Arch Gen Psychiatry. 1983 Jun;40(6):688-93
references.pmid: 6847336
references.citation: J Pharmacol Exp Ther. 1995 Dec;275(3):1090-8
references.pmid: 8531068
references.citation: Neurosci Lett. 2008 Jun 27;438(3):303-7
references.pmid: 18499349
references.citation: Lipids. 1999;34 Suppl:S251
references.pmid: 10419169