Effects of NMDA receptor modulation on hippocampal type 2 theta activity in rats

1. The present study was designed to investigate whether pharmacological modulation of N-methyl-D-aspartate (NMDA) receptor function could modify hippocampal type 2 theta activity in the dentate gyrus of rats. 2. The effects of pre-recording administration of d-cycloserine (DCS: 1.0, 3.0 and 9.0 mg/kg, i.p.), a partial agonist at the NMDA receptor associated glycine site, and MK-801 (0.1 mg/kg, i.p.), a noncompetitive NMDA receptor antagonist, were examined in freely moving rats. 3. Using adult Wistar rats, which had recording electrodes implanted unilaterally into the hilus of dentate gyrus, we recorded five 4 sec epochs of awake-immobility-related hippocampal EEG activity bands (1-20 Hz) 40 min after d-cycloserine and 2 hr after administration of MK-801. 4. In the off-line analysis, the spectral power and the frequency at the maximal theta power were calculated. 5. D-cycloserine (1.0-9.0 mg/kg) did not affect the frequency at the maximal theta power. However, the dose of 3.0 mg/kg, though not the 1.0 or 9.0 mg/kg doses, significantly increased the spectral power of the hippocampal immobility-related EEG activity. 6. In line with the previous findings, 0.1 mg/kg MK-801 decreased both the frequency at the maximal theta power as well as the spectral power of hippocampal type 2 EEG activity. 7. The present data show a clear relationship between NMDA receptors and hippocampal type 2 theta activity and suggest that the pharmacological modulation of the receptor function, using appropriate doses of glycine binding site agonist, d-cycloserine, may be a possible means to positively modulate the immobility-related hippocampal EEG activity.