Nitric oxide and glutamate interaction in the control of cortical and hippocampal excitability

Purpose: We investigated the role of nitric oxide (NO) as a new neurotransm itter in the control of excitability of the hippocampus and the cerebral co rtex, as well as the possible functional interaction between NO and the glu tamate systems. Methods: The experiments were performed on anesthetized rats. The bioelectr ical activities of the somatosensory cortex and the CA1 region of the hippo campus of these rats were recorded. Pharmacologic inhibition of NO synthase (NOS) through the nonselective and brain-selective inhibitors, N-nitro-L-a rginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), was performed. Results: The treatments caused the appearance of an interictal discharge ac tivity in both the structures. The latency of induction and the duration of the interictal discharge activity were strictly related to the dose of NOS inhibitor used. In some cases, after L-NAME treatment at high doses, it wa s possible to note spike and wave afterdischarge activity in the hippocampu s. All the NOS inhibitor-mediated excitatory effects were abolished by intr aperitoneal (i.p.) pretreatment with the N-methyl-D-aspartic acid (NMDA) re ceptor antagonists (DL-2-amino-5-phosphonovaleric acid, 2-APV; dizolcipine, MK-801) and partly suppressed after the i.p, injection of the non-NMDA ant agonist (6-cyano-7-nitroquinoxaline-2,3-dione; CNQX). Conclusions: All data showed that the reduction of NO levels in the nervous system causes the functional prevalence of the excitatory neurotransmissio n, which is probably due to an NMDA overactivity caused by the absence of t he NO-mediated modulatory action. Thus, it is possible to hypothesize a neu roprotective role for NO, probably through a selective desensitization of t he NMDA receptors.