Motor effects of acute and chronic inhibition of nitric oxide synthesis in mice

Abstract.

Rationale: Systemic injections of nitric oxide synthase (NOS) inhibitors have been shown to decrease exploratory behavior in rats. This effect may be related to motor impairments since these drugs can induce catalepsy in rodents. Objective: To compare the effects of two NOS inhibitors in tests aimed to investigate exploratory behavior and to assess motor control. Methods: The acute effects of the NOS inhibitors NG-nitro-L-arginine (L-NOARG, 10–80 mg/kg IP) and 7-nitroindazole (7-NIO, 3–30 mg/kg IP) on exploratory activity were analyzed in an open field arena. Drug effects on catalepsy were examined in the hanging-bar and wire-ring test. Footprint pattern after treatment with the two NOS inhibitors was evaluated and the results compared with those obtained with the dopamine D₂ receptor antagonist haloperidol (1–2 mg/kg IP). Sub-chronic (twice a day for 4 days) effects of L-NOARG (40 mg/kg) or 7-NIO (30 mg/kg) were also tested in the open field arena and catalepsy test. Results:L-NOARG and 7-NIO decreased locomotion and rearing in the open field arena. Both drugs induced catalepsy in the hanging-bar test but did not change footprint pattern. The cataleptic effect of L-NOARG in the hanging bar and wire-ring tests were highly correlated (r=0.927). The exploratory and cataleptic effects of L-NOARG and 7-NIO provided evidence for tolerance after sub-chronic treatment. Conclusion: These results confirm that inhibition of neuronal NO formation induces impairment of exploratory behavior. This effect does not seem to involve aspects evaluated by footprint analysis, such as weight support, trunk stability and foot placement. They could, however, be related to drug-induced catalepsy.