Abstracts

Based on amygdala kindling rates, we selectively bred rats to be seizure-prone or seizure-resistant. The strain differences in excitability are comorbid with important behavior/personality attributes. One of these reflects learning/attention problems with heightened activity in Fast rats, behaviors reminescent of ADHD in humans. The present experiments explore the learning impairments in Fast compared to Slow rats by measuring their controlling factors, distractability and tendency for hyperfocusing.
Naive male rats of the Fast and Slow strain were tested for escape speed and accuracy to a submerged platform in the Morris water maze (MWM) using protocols that measured spatial versus cued learning. In two versions of the spatial procedure, reference memory was measured in one, and working memory in the other, with or without pretraining procedures to familarize the rats with the task concepts. In other experiments, cued learning was assessed, where the location of the submerged platform was indicated by an overhanging cue. In one procedure, the predictive, overhanging cue was accompanied by a second, distracting cue that did not signal the platform. The distracting cue was presented either at the beginning or the end of the learning procedure. Lastly, activity and habituation were monitored in the open field over two days, in the presence or absence of a low dose of amphetamine (0.5mg/kg), which was introduced only on day one.
The Fast rats performed inferior to the Slow rats in acquisition of both the reference and working memory versions of the spatial MWM task. The disability in Fast rats was partially ameloriated by pretraining procedures, familarizing them with the task concepts. The Fast rats were also impaired in acquisition of the cued task, particularly when a distracting cue was available early in learning procedure. By contrast, when the distracting cue was available at the end of learning, Fast rats were not distracted by it, and remained completely focused on it, even when it was no longer predictive (hyperfocusing). Activity measurements indicated higher scores in Fast compared to Slow rats. However, on day two, Slow rats showed normal habitation, while Fast rats did not. In rats treated with amphetamine, the drug increased activity in Slow but not Fast rats, while on day two, without drug, both groups registered normal habituation.
The Fast rats showed spatial learning problems related to concept formation, which could be corrected with pretraining. In cued versions of the task, learning problems in Fast rats were accentuated by early distractability, but later cue fixation with no distractability. These results are analogous to humans with ADHD, who show distraction during initial learning, but hyperfocus in familar circumstances. Epilepy is up to 20 times more prevalent in those with ADHD than in others. Thus seizure-prone Fast rats provide an interesting new animal model of ADHD.
[Supported by: CIHR grants to DCM and HA]