THE ROLE OF NITRIC-OXIDE IN DIZOCILPINE-INDUCED IMPAIRMENT OF SPONTANEOUS-ALTERNATION BEHAVIOR IN MICE

We investigated the role played by nitric oxide in the dizocilpine-ind uced impairment of both spontaneous alternation behavior in a Y-maze a nd of performance in a multiple-trial passive avoidance task in mice. Dizocilpine (0.1 mg/kg) impaired the spontaneous alternation behavior and the retention of passive avoidance without affecting acquisition i n the multiple-trial passive avoidance task. N-G-nitro-L-arginine meth ylester (L-NAME), an inhibitor of nitric oxide (NO) synthase, dose-dep endently impaired the spontaneous alternation behavior, bur had no eff ect on either the acquisition or retention of passive avoidance. N-G-n itro-D-arginine methylester had no effect on either task. The inhibito ry effect of L-NAME on the spontaneous alternation behavior was comple tely reversed by the coadministration of L-arginine. Pretreatment with L-arginine ameliorated the dizocilpine-induced impairment of spontane ous alternation behavior, but not the impairment of the retention of p assive avoidance. S-Nitroso-N-acetylpenicillamine, a generator of NO, completely inhibited the dizocilpine-induced impairment of spontaneous alternation behavior. Finally, the impairment of spontaneous alternat ion behavior caused by dizocilpine was significantly diminished by pre treatment with dibutyryl cyclic GMP. These results suggest that, altho ugh N-methyl-D-aspartate receptors play a critical role in both spatia l working memory and long-term memory processes assessed by spontaneou s alternation behavior and the passive avoidance, respectively, differ ent neuronal mechanisms may be involved in these two processes. Furthe r, it is suggested that the NO/cyclic GMP system may play a role in sp atial working memory.