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Anticonvulsant effects of MK-801 and glycine on hippocampal afterdischarge
1Department of Medical Pharmacology and Toxicology, Texas A&M University, College Station 77843.
Abstract:
The effects of glycine and MK-801 on hippocampal seizure threshold and afterdischarge (AD) were determined in freely moving rats implanted with intracranial electrodes. The 0.25 mg/kg (ip) dose of MK-801 significantly reduced the primary hippocampal and cortical AD but induced neurological deficit in 4 of 16 rats. The 0.25 mg/kg MK-801 dose also significantly increased the seizure threshold as compared to the vehicle control treatment and reduced the rebound cortical AD as compared to the control (nondrug) seizure response. The 40 mmol/kg (po) glycine dose significantly reduced the rebound hippocampal and cortical AD without inducing neurological deficit. The 40 mmol/kg glycine dose did not significantly alter the response to the ineffective 0.125 mg/kg MK-801 dose. These results demonstrate the differential effects of MK-801 and glycine on primary and rebound hippocampal AD, respectively, which further establishes the independence of the hippocampal seizure AD parameters. The lack of interaction between MK-801 and glycine was unexpected considering that glycine potentiates MK-801 receptor binding as well as the activity of other anticonvulsants.
Insights
MK-801 reduced primary afterdischarge (AD) and increased seizure threshold in rats, while glycine reduced rebound AD without deficits. These findings highlight their distinct effects on hippocampal seizure parameters.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Epilepsy is characterized by recurrent seizures.
- Understanding the mechanisms of seizure generation and control is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the differential effects of glycine and MK-801 on hippocampal seizure threshold and afterdischarge (AD) in rats.
- To explore the independence of primary and rebound hippocampal AD parameters.
Main Methods:
- Freely moving rats were implanted with intracranial electrodes.
- Effects of systemically administered glycine (40 mmol/kg, po) and MK-801 (0.25 mg/kg, ip) on hippocampal and cortical AD and seizure threshold were assessed.
- Neurological deficits were monitored.
Main Results:
- MK-801 significantly reduced primary hippocampal and cortical AD and increased seizure threshold, but induced neurological deficits in some rats.
- Glycine significantly reduced rebound hippocampal and cortical AD without causing neurological deficits.
- Glycine did not alter the response to a sub-effective dose of MK-801.
Conclusions:
- MK-801 and glycine exhibit distinct effects on primary and rebound hippocampal AD, respectively.
- These findings support the independence of hippocampal seizure AD parameters.
- The lack of interaction between MK-801 and glycine was unexpected given known receptor interactions.