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MK-801 and NBQX prevent electrically induced status epilepticus
1Department of Pharmacology and Clinical Pharmacology, School of Medicine, University of Auckland, New Zealand.
Abstract:
MUSCARINIC, NMDA and metabotropic glutamate receptor antagonists were tested for anticonvulsant effects in a continuous hippocampal stimulation model in rats in order to identify the receptors involved in the initiation of electrically induced status epilepticus (SE). Whereas the muscarinic receptor antagonists scopolamine and atropine and the metabotropic receptor antagonist L(+)-2-amino-3-phosphonopropionic acid (AP3) did not affect SE initiation, the N-methyl-D-aspartate (NMDA) antagonist dizocilpine (MK-801) (1 mg kg-1 i.p.) and the non-NMDA ionotropic receptor antagonist 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (NBQX) (two doses of 50 micrograms i.c.v.) prevented the induction of SE. It has been shown in a previous study that non-NMDA ionotropic receptors are involved in SE maintenance and it is now suggested that activation of NMDA receptors may principally initiate electrically induced SE, although non-NMDA ionotropic receptors may also be involved.
Insights
N-methyl-D-aspartate (NMDA) receptor antagonists, but not muscarinic or metabotropic antagonists, prevented status epilepticus (SE) initiation in rats. This suggests NMDA receptors are key to initiating SE.
Area of Science:
- Neuroscience
- Pharmacology
- Epileptology
Background:
- Electrically induced status epilepticus (SE) is a model for studying seizure mechanisms.
- Understanding receptor involvement in SE initiation is crucial for developing treatments.
Purpose of the Study:
- To investigate the roles of muscarinic, N-methyl-D-aspartate (NMDA), and metabotropic glutamate receptors in the initiation of electrically induced status epilepticus (SE).
Main Methods:
- Tested various receptor antagonists, including scopolamine, atropine, L(+)-2-amino-3-phosphonopropionic acid (AP3), dizocilpine (MK-801), and 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (NBQX), in a rat model of continuous hippocampal stimulation.
- Assessed the effects of these antagonists on the initiation of SE.
Main Results:
- Muscarinic receptor antagonists (scopolamine, atropine) and the metabotropic receptor antagonist AP3 did not affect SE initiation.
- The NMDA receptor antagonist dizocilpine (MK-801) and the non-NMDA ionotropic receptor antagonist NBQX prevented SE induction.
- Previous studies indicated non-NMDA receptors are involved in SE maintenance.
Conclusions:
- NMDA receptor activation appears to be the principal initiator of electrically induced SE in this model.
- Non-NMDA ionotropic receptors may also contribute to SE initiation.
- These findings highlight the critical role of NMDA receptors in the early stages of SE.