Abstracts

Rationale: A great degree of comorbidity exists between epilepsy and childhood developmental disorders such as Attention Deficit/Hyperactivity Disorder (AD/HD) and the Autism Spectrum Disorders (ASD). Previous work from our laboratory has shown that rats selectively bred to be seizure prone (SP) versus seizure resistant (SR) exhibit behavioural features analogous to human cases of AD/HD and ASD, along with a marked developmental delay. Although the origin and significance of these behavioral patterns are not completely understood, they are suspected to partly result from structural deficits in important commissural systems such as the corpus callosum. Interestingly, several neuroanatomical features of SP rats coincide with what has been observed in ADHD/ASD patients, including a reduction in white matter volume that is most evident in the corpus callosum. Methods: In the current study, we compared rates of visuomotor development in SP and SR rats, their parental strains (Wistar and Long Evans Hooded), and in another putative model for AD/HD, the Spontaneously Hypertensive Rats (SHRs). Like our SP rats, SHRs are known to display AD/HD-like characteristics and to kindle more rapidly than the Wistar Kyoto strain from which they were derived. As rates of development are highly dependent on myelination patterns within the brain, we also examined potential structural differences in commissural tracts between SP and SR rats by looking at the interhemispheric transfer of a lipophillic fluorescent tracer in both strains. Results: Our results revealed a relative developmental delay in SHRs and SP rats compared to the other strains tested with respect to the acquisition of visuomotor tasks including the righting reflex, cliff avoidance and negative geotaxis. We also found that four days after an injection of the lipophillic tracer DiI (0.5ul) into the right amygdala, significantly more dye was present in the contralateral amygdala of SP versus SR rats, suggesting differential interhemispheric connectivity between the two strains. Conclusions: Collectively, these results suggest that SP rats may serve as an excellent model system for the ontogeny of AD/HD and ASD-like behaviours, particularly in individuals with comorbid epilepsy. Furthermore, this study may provide important insight into the role of major commissural systems in both the spread of seizure and brain laterality abnormalities reported in childhood developmental disorders.