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.
The present investigation was conducted to examine whether a reversible inhibitor of monoamine oxidase (MAO)-A, T-794, affects the shuttle-box escape deficit induced by transient middle cerebral artery (MCA) occlusion (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.
Kato
M
M
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Iwata
H
H
Okamoto
M
M
Ishii
T
T
Narita
H
H
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology*; D003863:Depression / Q000209:etiology*; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000187:drug effects*; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats
D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase