Nitric oxide is involved in the expression of neocortical spike-and-wave spindling episodes in DBA/2J mice

This study investigated the possible role of nitric oxide (NO) in the development of neocortical spike-and-wave spindling episodes (S&W) of DBA/2J mice. The administration of distilled water did not modify either the number or duration of S&W in DBA/2J mice during the whole recording period (240 min). L-N(G)-nitro arginine methyl ester (L-NAME) (3-300 microg/mouse, i.c.v.) dose-dependently reduced the S&W of DBA/2J mice. This effect appeared 30 min after drug administration and lasted for the duration of the recording period (240 min). In addition, L-NAME treatment did not induce significant alterations of stereotyped behaviour such as licking, sniffing, chewing or tremors of the head and body and behavioural excitability, whereas the electroencephalogram desynchronized pattern was also significantly reduced. By contrast D-N(G)-nitro arginine methyl ester at the same doses did not affect S&W of mice. The inhibitory effect of L-NAME on S&W of mice was dose-dependently reversed by L-arginine (L-ARG, 3-300 microg/mouse, i.c.v.) but not by D-arginine. Finally, glyceryl trinitrate on its own (3-300 microg/mouse, i.c.v.) significantly increased the S&W of mice and it was also able to reverse the inhibition on S&W of mice operated by L-NAME. These results provide evidence that NO may play a significant role in the development of brain excitability.