CHRONIC ADMINISTRATION OF A NITRIC-OXIDE SYNTHASE INHIBITOR, N-OMEGA-NITRO-L-ARGININE, AND DRUG-INDUCED INCREASE IN CEREBELLAR CYCLIC-GMP IN-VIVO

N(omega)-nitro-L-arginine (N(G)-nitro-L-arginine) is a potent nitric o xide synthase inhibitor which crosses the blood brain barrier and does not undergo extensive metabolism in vivo. In this study, effect of ch ronic pretreatment of N(omega)-nitro-L-arginine (75 mg/kg, i.p., twice daily for 7 days) on the harmaline- (100 mg/kg, s.c.), picrotoxin- (4 mg/kg, s.c.), pentylenetetrazole- (50 mg/kg, i.p.), and L-glutamic ac id- (400 mug/10 mul/mouse, i.c.v.) induced increase in cerebellar cGMP was assessed. All the four drugs produced significant increase in cer ebellar cGMP in vehicle pretreated control animals. Cerebellar cGMP in crease induced by harmaline, picrotoxin, and L-glutamic acid was atten tuated in N(omega)-nitro-L-arginine pretreated animals. These results indicate that in vivo cerebellar cGMP levels are increased by the prot otype excitatory amino acid receptor agonist, L-glutamic acid and also by the drugs which augment the excitatory amino acid transmission. Fu rthermore, parenteral chronic administration of N(omega)-nitro-L-argin ine blocks NO synthase in the brain and hence cerebellar cGMP response in chronic N(omega)-nitro-L-arginine treated animals could be used as a tool to assess the physiological functions of nitric oxide in vivo.