Catalepsy induced by intra-striatal administration of nitric oxide synthase inhibitors in rats

Systemic administration of nitric oxide synthase (NOS) inhibitors induces catalepsy in a dose-dependent manner in male Albino-Swiss mice. The objective of the present work was to investigate if similar effects occur in rats and if these effects are centrally mediated. The results showed that systemic administration of N(G)-nitro-L-arginine (L-NOARG, 40-160 mg/kg, i.p.), a non-selective NOS inhibitor, induced catalepsy in rats. Similar effects were found after intracerebroventricular (i.c.v.) injection of L-NOARG (50-200 nmol) or N(G)-nitro-L-arginine methylester (L-NAME, 100-200 nmol). The dose-response curve of the former compound, however, had an inverted U shape. The effect of L-NOARG (100 nmol, i.c.v.) was completely prevented by pre-treatment with L-arginine (300 nmol, i.c.v.) but not by D-arginine (300 nmol, i.c.v.). Intra-striatal injection of N(G)-monomethyl-L-arginine (L-NMMA, 100 nmol), 7-nitroindazole (7-NIO, 100 nmol), L-NOARG (25-100 nmol) or L-NAME (50-200 nmol) also induced catalepsy. Similar to i.c.v. administration, the latter two compounds produced bell-shaped dose-response curves. The cataleptic effect of intra-striatal administration of L-NAME (100 nmol) was reversed by local treatment with L-arginine (100 nmol). These results suggest that interference with the striatal formation of nitric oxide may induce significant motor effects in rats.