<原著>抗コリン作動薬長期投与後のラット空間学習の成立過程と海馬内の形態学的変容との関連
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A large number of studies have examined the inhibitory effects of anticholinergic drugs (scopolamine ; antimuscarinic receptor agent) on spatial learning. However, almost all of these studies have observed only the transient or short-term effects of scopolamine. The present study examined the acquisition of spatial learning using the Morris water maze after the chronic: injection of scopolamine into rats. Scopolamine was injected intraperitoneally 0.4 mg/kg/day (SP I group) orlmg/kg/day (SPI1 group) for 14 days and also injected subcutaneously by means of osmotic pump 2.5 μl/hr (SP III group) for 28 days before starting the task of spatial learning of the Morris water maze. These groups were compared to the control groups with the same dose of physiological saline. All subjects were trained to learn the position of a hidden escape platform (place learning) through four trials per day, with an intertrial interval of approximately 10 minutes, for a total of 4 days. The location of the hidden escape platform remained constant and, on each trial, rats swam for 90 seconds or until they found the platform. The starting location varied randomly across the trials. On the fifth day, the platform was retracted, and rats swam for 60 seconds as a probe test. Then the cue learning was tested subsequently in a single session of 4 trials in which rats swam to the visible escape platform that protruded above the surface of the pool, for 90 seconds on each trial. After the completion of the behavioral testing, the rat brains were perfused with a 0.1% sodium sulphide, followed by perfusion with a 8% formaline in 0.1 M phosphate buffer and cut at the thickness of 60 μm. Serial sections were processed for Timm staining, in order to examine the relationship between learning ability and the morphological changes in the hippocampal dentate mossy fiber terminals. In the SP III group, the escape latency to the hidden platform significantly increased only in the early stage of the place learning (2nd and 5th trials). Additionally, the volume of the hippocampal mossy fiber terminals at the rostral portion increased exclusively in these learning impaired rats of the SP III group but not in the unimpaired and control rats. These results suggested that the chronic injection of scopolamine might induce the neurogenesis of the rostral part of the dentate granule cells and also augment the volume of the mossy fiber terminals to supplement the cholinergic depletion, although there was not a severe inhibitory effect on the acquisition of the spatial learning.
- 福井大学の論文
- 2002-12-20
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