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Effect of cyclothiazide on efflux of cGMP in the hippocampus of freely-moving rats

Objective and Methods The effects of cyclothiazide on cGMP efflux were determined by in vivo microdialysis in the rat hippocampus. Results When α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) 150 μmol/L was locally infused into the hippocampus, the cGMP level only increased most animals to some extent, but not high enough for statistics. The local infusion of cyclothiazide 300 μmol/L into the rat hippocampus, a blocker of AMPA receptor desensitization, elicited the elevation of cGMP levels. The effect of cyclothiazide was blocked by local administration of the NO synthase inhibitor N G-nitro-L-arginine 150 μmol/L or the selective inhibitor of soluble guanylyl cyclase 1H-oxadiazoloquinoxalin-1-one(ODQ)50 μmol/L. Conclusion These results suggest that AMPA receptors related to the NO/cGMP pathway in the hippoca mpus are tonically activated and kept in a desensitized state by endogenous glutamate.