Abstract
Idebenone (6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone) is a benzoquinone that has been shown to improve cognitive function in animals subjected to cerebral ischemia and in rats with lesions of the basal forebrain cholinergic system. Because the cognitive deficits observed in aged rats have been associated with decreased cerebral blood flow and basal forebrain cholinergic dysfunction, it was hypothesized that IDE might improve cognition in aged animals. In the present study, the effects of idebenone on cognitive function in aged Long-Evans rats were assessed using a battery of tests that evaluated attention, habituation, and spatial learning. Selective attention was assessed using an overshadowing paradigm, where IDE (30 mg/kg, IP) was injected 30 min prior to compound cue exposure. IDE enhanced the overshadowing effect in aged rats. The Morris water maze was used to assess spatial learning, where IDE (3 mg/kg, IP) was injected daily throughout the course of training. IDE did not improve the impaired performance of aged rats in the Morris task. Habituation was tested by measuring recovery from gustatory neophobia. IDE (30 mg/kg, IP) was injected 30 min prior to the first exposure to the novel taste. IDE normalized habituation rate in aged rats. It was concluded that IDE improves some forms of acquisition in aged rats, and may do so by decreasing general reactivity to novel stimuli.
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