Nitric Oxide and Glutamate Interaction in the Control of Cortical and Hippocampal Excitability

Abstract

Summary: Purpose:We investigated the role of nitric oxide (NO) a5 a new neurotransmitter in the control of excitability of the hippocampus and the cerebral cortex, as well as the possible functional interaction between NO and the glutamate systems.method,^: The experiments were performed on anesthetized rats. The bioelectrical activities of the somatosensory cortex and the CAI region of the hippocampus of these rats were recorded. Pharmacologic inhibition of NO synthase (NOS) through the nonselective and brain-selective inhibitors, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), was performed. Results:The treatments caused the appearance of an interictal discharge activity 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 was possible to note spike and wave afterdischarge activity in the hippocampus. All the NOS inhibitor-mediated excitatory effect? were abolished by intraperitoneal (i.p.) pretreatment with the Nmethyl-D-aspartic acid (NMDA) receptor antagonists (DL-2-amino-5-phosphonovaleric acid, 2-APV; dizolcipine, MK-80 1) and partly suppressed after the i.p. injection of the non-NMDA antagonist (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 neurotransmission, which is probably due to an NMDA overactivity caused by the absence of the NO-mediated modulatory action. Thus, it is possible to hypothesize a neuroprotective role for NO, probably through a selective desensitization of the NMDA receptors.

Effects of L-Arginine on Penicillin-Induced Epileptiform Activity in Rats

“…Competitive inhibition on NMDA receptors: As already known, NMDA receptor activation causes NO production and NO exerts a negative feedback inhibition on NMDA receptors in normal physiological conditions (22,24). L-Arginine may also stimulate the production of NO and hence block the NMDA receptors.…”

“…NO is considered as a retrograde messenger involved in glutamatergic neurotransmission in the CNS (21). NO inhibits the epileptiform activity probably by blocking the NMDA receptors (22,23). The inhibitory effects of NO on epileptiform activity may occur via at least three different mechanisms:…”

Nitric oxide-active compounds modulate the intensity of glutamate-evoked responses in the globus pallidus of the rat

“…NO is a versatile gaseous molecule, able to modulate both the neuronal excitability and the release of neurotransmitters in many structures of the CNS of mammalians (Cudeiro et al, 1997;Shaw and Salt, 1997;Ferraro et al, 1999;Trabace and Kendrick, 2000;Prast and Philippu, 2001;Ahern et al, 2002;Li et al, 2004;Garthwaite, 2008). Clear NO-mediated actions have been shown in the BG (Cox and Johnson, 1998;Calabresi et al, 1999;Centonze et al, 2001): in this regard, strong modulatory effects exerted by NO-active drugs on the bioelectric activity of striatal, pallidal, subthalamic and nigral cells have been recently demonstrated (Sardo et al, 2002a(Sardo et al, ,b, 2003(Sardo et al, , 2006aCarletti et al, 2009), as well as a marked influence of NOactive drugs on GABA-and GLU-evoked responses in the STN .…”

The Effects of Pregabalin on Cerebral Cortical Oxidative Stress of Rats on Pentylenetetrazole Induced Epileptic Seizure

“…So, NMDA receptor activities decrease and the neurons are saved from overstimulation. [27,30] Ferraro et al [28] showed that decreasing NO levels affected the stimulation of the NMDA receptors and increased the excitatory neurotransmission in the brain cortex and hippocampus.…”

“…NO may exert proconvulsive or neurotoxic effects by increasing glutamate, and may produce anticonvulsive or neuroprotective influences by supplying GABA to the tissues. [28] Noh et al [29] reported that the ketogenic diet was effective in experimental nitric oxide synthase (NOS) to knock out the mouse's hippocampus and as an antiepileptic via the releasing of the endogenous NO levels to increase the expression of NOS. Stimulation of the NMDA receptors causes NO production.…”