Anticonvulsant effects of MK-801 and glycine on hippocampal afterdischarge

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.