Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice
Section snippets
Materials
The animals used in this study were male mice of the ddY strain (six weeks old; Nihon SCL, Shizuoka, Japan) weighing 30–33 g. All animals were kept in a regulated environment (23±0.5°C; 50±0.5% humidity) with a 12-h light/dark cycle (light on between 9.00 a.m. and 9.00 p.m.) and had free access to food and water. l-NAME, l-arginine, and Br-cGMP were purchased from Sigma (St Louis, MO, U.S.A.). Dizocilpine [(+)-MK-801] and 7-NI were obtained from Research Biochemicals International (Natick, MA,
Effects of dizocilpine, NG-nitro-l-arginine methyl ester, and 7-nitro indazole on spontaneous alternation behavior
During the 8-min session, vehicle-treated control mice showed approximately 30 arm entries and 73% spontaneous alternation (Fig. 1 and Table 1). Dizocilpine and l-NAME impaired the spontaneous alternation in a dose-dependent manner, significantly inhibiting this behavior at doses of 0.1 mg/kg and 100 mg/kg, respectively. Dizocilpine (0.1 mg/kg), but not l-NAME, significantly increased the number of arm entries (Fig. 1). 7-NI also dose-dependently impaired the spontaneous alternation behavior (F3,
Discussion
We have previously shown that dizocilpine and l-NAME impaired the spontaneous alternation behavior of mice in the Y-maze.[53]It is known that NO synthase inhibitors such as l-NAME cause hypertension following systemic injection.[42]In contrast, 7-NI, at doses up to 80 mg/kg, is reported to have no effect on mean arterial pressure in the anesthetized mouse.[33]Since we observed that 7-NI significantly and dose-dependently impaired the spontaneous alternation behavior at doses up to 75 mg/kg, it is
Conclusions
The present results suggest that reduction in NO/cGMP formation in the brain may be responsible for the dizocilpine-induced impairment of spatial working memory. Furthermore, the results suggest that acute inhibition of NO production has no effect on monoamine and acetylcholine metabolism in the brain.
Acknowledgements
This study was supported, in part, by an SRF Grant for Biomedical Research and by grants from the Japanese Ministry of Health and Welfare Foundation for Gerontological Science Research (94A-2405), the Uehara Memorial Foundation, the Ishida Foundation, and the Ministry of Education, Science and Culture, Japan (No. 07557009).
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2016, Handbook of Behavioral NeuroscienceCitation Excerpt :Magnetometer-based HTR detection may provide a high-throughput, semiautomated assay for this behavior, and offer several advantages over traditional assessment methods (Halberstadt & Geyer, 2013a). The Y-maze test is widely used for the evaluation of WM (or short-term memory) and requires immediate sequential association of movements and different visual stimuli (Nabeshima et al., 1994; Yamada et al., 1996). The water-finding test is used to evaluate WM as well as latent learning (Nabeshima et al., 1994).