Open AccessGTS-21, a Nicotinic Agonist, Attenuates Multiple Infarctions and Cognitive Deficit Caused by Permanent Occlusion of Bilateral Common Carotid Arteries in Rats
Author(s) -
Masato Nanri,
Hidekazu Miyake,
Yukihisa Murakami,
Kinzo Matsumoto,
Hiroshi Watanabe
Publication year - 1998
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.78.463
Subject(s) - hippocampus , cognitive deficit , medicine , striatum , water maze , morris water navigation task , ischemia , agonist , radial arm maze , anesthesia , white matter , occlusion , nicotinic agonist , endocrinology , psychology , cognition , neuroscience , magnetic resonance imaging , receptor , cognitive impairment , working memory , dopamine , disease , radiology
We examined the effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride], a nicotinic agonist, on histopathological changes of the brain and radial maze learning performance in rats with permanent occlusion of the bilateral common carotid arteries (2VO) and elucidated whether this compound has a protective effect against the neuronal degeneration and spatial cognitive deficit caused by chronic ischemia. Rats were administered GTS-21 (1 and 10 mg/kg, p.o.) or vehicle 24 hr and 30 min before the 2VO operation and then once daily for 2 months after the operation. The 2VO rats given vehicle had multiple infarctions in the cerebral cortex, hippocampus and striatum and rarefaction in the white matter at 2 months after the operation, although the number and distribution of infarctions varied among individual animals. In addition, the 2VO rats given vehicle showed a higher rate of errors in the acquisition trials of the 8-arm radial maze task than sham-operated controls. However, 2VO rats treated with GTS-21 (1 and 10 mg/kg, p.o.) showed significantly decreased neuropathological changes and less errors in the acquisition trials compared to the vehicle-treated 2VO rats. These results indicate that GTS-21 attenuates impairment of spatial cognitive deficit and progressive neuronal degeneration induced by 2VO and suggest that this compound is beneficial for the treatment of neurodegenerative diseases following chronic cerebral hypoperfusion.