7-NITROINDAZOLE AND METHYLENE-BLUE, INHIBITORS OF NEURONAL NITRIC-OXIDE SYNTHASE AND NO-STIMULATED GUANYLATE-CYCLASE, BLOCK MK-801-ELICITEDBEHAVIORS IN MICE

We examined the abilities of 7-nitroindazole and methylene blue, inhib itors of the neuronal isoform of nitric oxide synthase (NOS) and nitri c oxide-stimulated guanylate cyclase activity respectively, to attenua te explosive episodic jumping behavior(s) (''popping'') elicited by MK -801 in mice. MK-801, like phencyclidine (PCP), is a high-affinity, no ncompetitive antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. We have postulated that MK-801-elicited popping be havior in mice represents an animal model of schizophrenia, because po pping behavior is markedly inhibited/antagonized by both typical and a typical antipsychotic drugs. In the present study, popping behavior in duced by MK-801 was measured using an automated detection system that quantifies vertical displacements on the testing platform. 7-Nitroinda zole (100 mg/kg) and methylene blue (32 and 100 mg/kg) significantly r educed the number and force of MK-801-elicited popping behavior. Mouse rotorod performance did not differ between animals receiving 7-nitroi ndazole, methylene blue, or their respective vehicles, suggesting that attenuation of MK-801-elicited popping behavior was not due to either sedation or ataxia caused by 7-nitroindazole or methylene blue. Our f indings suggest that nitric oxide may in part, mediate behaviors induc ed by NMDA receptor antagonists, like MK-801, and that inhibitors of N OS may have antipsychotic actions.