Effects of Nitric Oxide on Morris Water Maze Performance in Rats: Correlation with cGMP Levels

Abstract

The relationship between cGMP (guanosine 3′,5′ cyclic monophosphate) and CNS amino acid neurotransmission systems have been known since two decades and glutamate has been shown to increase cGMP levels in mouse striatal slices (Ferandelli JA et al., 1973). Activation of glutamate receptors triggers biochemical events stimulating calcium influx (Wroblewski JT et al., 1985) and cGMP accumulation (Novelli A et al., 1987). NO (nitric oxide) is a novel biological messenger molecule in the CNS which is enzymatically formed from L-Arginine by nitric oxide synthase (NOS), a Ca²⁺-Calmodulin requiring enzyme; citrulline is the co-product (Garthweite J 1991). Glutamate and N-methyl-D-aspartate (NMDA) receptor activation stimulate arginine-citrulline formation and increase cGMP levels in the cerebellum; L-N^G-monomethyl-arginine (L-NMMA) inhibits NOS and prevents the stimulation of cGMP formation (Bredt DS and Snyder SH 1989, Garthweite J et al 1989). NMD A receptor activation has thus been linked to NO.