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Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

Kine S Dervola1*, Bjørg Å Roberg1, Grete Wøien2, Inger Lise Bogen1, Torbjørn H Sandvik4, Terje Sagvolden2, Christian A Drevon3, Espen Borgå Johansen5 and Sven Ivar Walaas1

Author Affiliations

1 Department of Biochemistry, Institute of Basic Medical Science, Faculty of Medicine, University of Oslo, Oslo, Norway

2 Department of Physiology, Institute of Basic Medical Science, Faculty of Medicine, University of Oslo, Oslo, Norway

3 Department of Nutrition, Institute of Basic Medical Science, Faculty of Medicine, University of Oslo, Oslo, Norway

4 Institute of Psychology, University of Oslo, Oslo, Norway

5 Oslo and Akershus University College of Applied Sciences, Oslo, Norway

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Behavioral and Brain Functions 2012, 8:56  doi:10.1186/1744-9081-8-56

Published: 10 December 2012

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.

Keywords:
Omega-3; ADHD; Behaviour; Dopamine; Serotonin; Glutamate; Neostriatum