title: Marine Ο-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD.
abstract: BACKGROUND
  Previous reports suggest that omega-3 (n-3) polyunsaturated fatty acids (PUFA) supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD.
  
  
  METHODS
  We used spontaneously hypertensive rats (SHR). SHR dams were given n-3 PUFA (EPA and DHA)-enriched feed (n-6/n-3 of 1:2.7) during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY) control rats were given control-feed (n-6/n-3 of 7:1). During postnatal days (PND) 25-50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55-60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography.
  
  
  RESULTS
  n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover.
  
  
  CONCLUSIONS
  Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms in both sexes.
authors.affiliation: Department of Biochemistry, Institute of Basic Medical Science, Faculty of Medicine, University of Oslo, Oslo, Norway. k.s.n.dervola@medisin.uio.no
authors.forename: Kine S
authors.initials: KS
authors.lastname: Dervola
authors.forename: Bjørg A
authors.initials: BA
authors.lastname: Roberg
authors.forename: Grete
authors.initials: G
authors.lastname: Wøien
authors.forename: Inger Lise
authors.initials: IL
authors.lastname: Bogen
authors.forename: Torbjørn H
authors.initials: TH
authors.lastname: Sandvik
authors.forename: Terje
authors.initials: T
authors.lastname: Sagvolden
authors.forename: Christian A
authors.initials: CA
authors.lastname: Drevon
authors.forename: Espen Borgå
authors.initials: EB
authors.lastname: Johansen
authors.forename: Sven Ivar
authors.initials: SI
authors.lastname: Walaas
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001289:Attention Deficit Disorder with Hyperactivity / Q000178:diet therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012054:Reinforcement, Psychology; D012727:Sex Characteristics
chemical_list: D015525:Fatty Acids, Omega-3; D018377:Neurotransmitter Agents