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Convulsive seizures induced by N-methyl-D-aspartate microinjection into the mesencephalic reticular formation in rats
1Department of Psychiatry and Neurology, Asahikawa Medical College, Midorigaoka higashi 2-1-1-1, 078-8510, Asahikawa, Japan. ishimoto@asahikawa-med.ac.jp
Abstract:
Effects of microinjections of a single 2 or 10 nmol dose of N-methyl-D-aspartate (NMDA) into the unilateral mesencephalic reticular formation (MRF) on behavior and electroencephalogram were examined in rats (n=18) during a 15 min period (Exp. 1), and subsequent effects of sound stimulation with key jingling applied at 15, 30, and 45 min after the injections were observed (Exp. 2). The microinjections of 2 nmol dose of NMDA (n=10) induced hyperactivity (9 of 10 rats) and running/circling (8 of 10 rats) in Exp. 1, and hyperactivity (3 of 10 rats) in Exp. 2. Moreover, the microinjections of 10 nmol dose of NMDA (n=8) induced not only hyperactivity (8 of 8 rats) and running/circling (7 of 8 rats) but also generalized tonic-clonic seizures (GTCS) (5 of 8 rats) in Exp. 1; these seizure patterns were also elicited by sound stimulation in Exp. 2. The seizure patterns were accompanied by electroencephalographic seizure discharges in the MRF and the motor cortex. In contrast, the control group rats (n=10) which received a single dose of saline microinjection into the unilateral MRF showed no behavioral or electroencephalographic changes in both Exp. 1 and 2. These findings suggest that the MRF has an important role in the development of GTCS, which follows hyperactivity and running/circling, and that potentiation of excitatory neurotransmission in the MRF participates in the development of audiogenic seizures as well as GTCS.
Insights
Microinjections of N-methyl-D-aspartate (NMDA) into the mesencephalic reticular formation (MRF) induced hyperactivity and seizures in rats. These findings highlight the MRF
Area of Science:
- Neuroscience
- Neuropharmacology
- Behavioral Neuroscience
Background:
- The mesencephalic reticular formation (MRF) is implicated in motor control and arousal.
- Excitatory neurotransmission plays a critical role in brain function and neurological disorders.
Purpose of the Study:
- To investigate the role of the mesencephalic reticular formation (MRF) in seizure development.
- To examine the effects of N-methyl-D-aspartate (NMDA) on behavior and electroencephalogram (EEG) in rats.
Main Methods:
- Rats received microinjections of NMDA (2 or 10 nmol) or saline into the unilateral MRF.
- Behavioral changes and EEG activity were monitored for 15 minutes post-injection.
- Sound stimulation was applied to assess audiogenic seizure susceptibility.
Main Results:
- NMDA microinjections induced hyperactivity, running/circling, and generalized tonic-clonic seizures (GTCS).
- Higher NMDA doses (10 nmol) were more likely to cause GTCS.
- Seizures were accompanied by EEG discharges in the MRF and motor cortex.
- Sound stimulation elicited seizures in NMDA-treated rats.
Conclusions:
- The MRF plays a significant role in the development of GTCS.
- Potentiation of excitatory neurotransmission in the MRF contributes to audiogenic and GTCS.
- NMDA-induced hyperactivity and circling may precede seizure development.