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Aggravation of DMCM-induced seizure by nitric oxide synthase inhibitors in mice
1Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Abstract:
The present study investigated the effects of nitric oxide synthase (NOS) inhibitors on the seizure threshold of DMCM in mice. The seizure threshold of DMCM was evaluated using an intravenous infusion technique. The threshold of DMCM was significantly decreased by pretreatment with N-nitro-L-arginine (NOARG; 8 mg/kg) and N-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg), but not with D-NAME. Furthermore, these NOS inhibitors also decreased the threshold for pentylenetetrazole-induced seizure. However, the threshold for caffeine-induced seizure was not affected by NOARG. These results suggest that the endogenous NO system may play an important role in the expression of seizure by GABA(A) receptor inhibitory agents (DMCM and PTZ).
Insights
Nitric oxide synthase (NOS) inhibitors reduced seizure thresholds in mice treated with DMCM and pentylenetetrazole. This suggests endogenous nitric oxide plays a role in seizures induced by GABA(A) receptor inhibitors.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- GABA(A) receptors are crucial inhibitory neurotransmitter receptors in the brain.
- Nitric oxide (NO) is a signaling molecule implicated in various physiological and pathological processes, including neurological disorders.
Purpose of the Study:
- To investigate the role of nitric oxide synthase (NOS) in modulating seizure susceptibility.
- To determine the effect of NOS inhibition on seizure thresholds induced by specific agents.
Main Methods:
- Mice were administered DMCM (a GABA(A) receptor antagonist) or pentylenetetrazole via intravenous infusion to induce seizures.
- Mice were pretreated with NOS inhibitors: N-nitro-L-arginine (NOARG) and N-nitro-L-arginine methyl ester (L-NAME).
- Seizure thresholds were determined by measuring the dose of the convulsant agent required to elicit seizure activity.
Main Results:
- Pretreatment with NOARG and L-NAME significantly lowered the DMCM-induced seizure threshold.
- NOS inhibitors also decreased the threshold for pentylenetetrazole-induced seizures.
- N-nitro-L-arginine did not affect the seizure threshold for caffeine-induced seizures.
Conclusions:
- Endogenous nitric oxide system activity is important for the expression of seizures induced by GABA(A) receptor inhibitory agents like DMCM and pentylenetetrazole.
- These findings highlight a potential role for targeting the NO pathway in managing certain types of seizures.
