Although N-methyl-D-aspartate (NMDA) receptors of the hippocampus are mainly associated with learning and memory that might occur "online" during sharp waves (SPWs) and theta-rhythm, the participation of hippocampal NMDA receptors in sleep-related processes has not been well studied. In this study, the activity of sleep episodes, hippocampal SPWs and theta-rhythm were recorded in rats received a repeated infusion of NMDA receptor antagonist, D,L-2-amino-5-phosphonopentanoic acid (AP5), into the lateral ventricle in a 5-h daytime sleep. The first trial AP5 infusion (30 mM/2 mu l) did not change measures of the activity of slow wave sleep (SWS), paradoxical sleep (PS) and awake episodes, but induced a delay in the latency of the first onset of PS; in the hippocampal EEG, it increased the amplitude of SPWs within SWS and shifted the amplitude/spectral power of theta-rhythm from high to low frequency within PS. The repeated AP5 infusion augmented the activity of SWS, and impaired PS and awake episodes; in the EEG-sleep picture, it maintained high scores of SPWs with the complete blockade of theta-rhythm generation. When AP5 rat was woken, the theta-rhythm was seen during exploratory behavior. These findings provide evidence that hippocampal NMDA receptors via SPWs or directly associated with the synaptic events of theta-rhythm generation are critical for the PS activities. (c) 2005 Elsevier Inc. All rights reserved.