Focal Cerebral Ischemia-Induced Escape Deficit in Rats Is Ameliorated by a Reversible Inhibitor of Monoamine Oxidase-A : Implications for a Novel Animal Model of Post-Stroke Depression

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The present investigation was conduceted to examine whether a reversible inhibitor of monamine oxidase (MAO)-A, T-794,affects the shuttle-box escape deficit induced by transient middle cerebral artery (MCA) occulusion (MCAO). MCA-occluded and sham-operated rats (surgery on day 0) were subjected to daily shuttle-box session from day 7 to 9 (training series) and from day 13 to 15 (test series) and received twice daily administration of T-794 (10 mg/kg p.o., b.i.d.) or vehicle from the evening of day 9. In the final shuttle-box session of test series (day 15), while MCA-occluded-vehicle-treated rats showed significantly more escape failures than sham-operated-vehicle-treated rats, the failures made by MCA-occluded rats were significantly decreased by T-794 to the level of the sham-operated group. Additionally, biochemical examination was conducted after behavioral evaluation to examine possible involvement of the brain monoamine system in the observed behavioral syndrome. In occluded hemisphere of MCA-occluded rats, catecholamine levels were decreased and ratios of deaminated metabolite to corresponding monoamine were increased compared with the respective values of the sham-operated group, and these changes were reversed by T-794. Results are discussed in terms of possible relevance of the MCAO-induced escape deficit to post-stroke depression.
公益社団法人日本薬学会の論文
2000-04-01