Abstracts

Epilepsy and attention deficit hyperactivity disorder (ADHD) have recently been established as true co-morbid disorders (Kanner et al., 2003). Fast (seizure-prone) and Slow (seizure-resistant) kindling inbred rat strains, derived via selective breeding, serve as an excellent model for seizure susceptibility, yet Fast rats also exhibit adult behavioral profiles indicative of relative ADHD-like behaviors. In order to begin to explore the genetic basis for relative seizure susceptibility and ADHD-like behaviors in Fast rats, we interbred the two strains and examined adult offspring (F1 hybrid) behaviors., Male Fast rats were bred with female Slow rats to create an F1 population of hybrid pups. Offspring generated by breeding Fast males with Fast females or Slow males with Slow females served as control populations. As adults, all rats were compared in several behavioral paradigms known to elicit differential responses from Fast and Slow rats including kindling, restraint and open field. Water consumption was also compared. Finally, blood was extracted from all rats and levels of non-esterfied fatty acids (NEFA), known to be deficient in Fast rats, were compared., F1 hybrids showed water consumption and kindling rates that were indistinguishable from Fast rats. Remarkably, however, hybrids exhibited behaviors that were near identical to Slow rats in both the open field and restraint paradigm. Thus, hybrids appear to have maintained the relative seizure susceptibility, but not the ADHD-like behaviors, of their Fast fathers. Further, blood analysis showed that F1 hybrids exhibited the relatively higher NEFA levels characteristic of Slow rats., Results suggest that a primary dominant or semi-dominant genetic effect mediates the differences in kindling rate and water intake between Fast and Slow rats. Lack of a similar finding for other behavioral traits may be due to a maternal genetic influence or the influence of unknown environmental factors. Interestingly, NEFA was higher in hybrids and Slow rats compared to Fast rats, thus implying a link between ADHD-like behaviors and a relative NEFA deficiency., (Supported by CIHR and NSERC to DCM.)