Chronic omega-3 supplementation in seizure-prone versus seizure-resistant rat strains: a cautionary tale.
Several studies have shown fatty acid supplementation to be efficacious in the treatment of attention deficit hyperactivity disorder/autism spectrum disorder (ADHD/ASD) and epilepsy. Interestingly, rats bred to be seizure-prone (Fast), unlike those bred for seizure-resistance (Slow), naturally exhibit behaviors and physiology reminiscent of ADHD/ASD in humans, suggesting a fundamental link between seizure disposition and these developmental disorders. To determine whether chronic omega-3 supplementation might ameliorate ADHD-like behaviors in the seizure-prone rat strain and/or alter natural predispositions for or against seizure in either strain, Fast and Slow weanlings were maintained on a control or omega-3-supplemented diet. As adults, rats were tested in paradigms known to elicit ADHD-like behaviors from Fast rats and then kindled from the amygdala to assess relative seizure disposition. While omega-3 supplementation did not significantly alter the relative hyperactivity, learning deficits or heightened seizure sensitivity naturally exhibited by Fast rats, it dramatically reduced their impulsivity to Slow-like levels. In contrast, typical behavioral patterns in Slow rats were largely unaffected by omega-3 supplementation yet their proclivity for seizure was greatly increased. This heightened vulnerability to seizure in Slow rats was paralleled by a drop in circulating plasma non-esterified fatty acids (NEFA) to match levels normally observed in Fast rats. These findings suggest a delicate balance between seizure predisposition and ADHD-like behaviors that can be influenced by omega-3 treatment. Further, a relationship between circulating NEFA levels and seizure susceptibility has surfaced that advocates caution when treating different genetic backgrounds with omega-3 fatty acids.
Gilby
K L
KL
Institute of Neuroscience, Life Sciences Research Center, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1S 5B6. krista_gilby@carleton.ca
Jans
J
J
McIntyre
D C
DC
D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000523:psychology; D001522:Behavior, Animal; D001835:Body Weight; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000523:psychology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004326:Drinking; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007696:Kindling, Neurologic; D008297:Male; D051381:Rats; D012640:Seizures / Q000235:genetics / Q000517:prevention & control* / Q000523:psychology
D005230:Fatty Acids, Nonesterified; D015525:Fatty Acids, Omega-3