INJECTIONS OF EXCITATORY AMINO-ACID ANTAGONISTS INTO THE MEDIAN RAPHENUCLEUS PRODUCE HIPPOCAMPAL THETA-RHYTHM IN THE URETHANE-ANESTHETIZEDRAT

The median raphe nucleus (MR) exerts a pronounced desynchronizing infl uence on the hippocampal EEG. MR stimulation disrupts theta, while MR lesions produce constant uninterrupted theta. The MR receives pronounc ed excitatory amino acid (EAA)-containing afferents that have been imp licated in several MR-mediated behaviors. The present study examined t he effects on the hippocampal EEG of MR injections of the following EA A antagonists in the urethane-anesthetized rat: 2-amino-7-phosphonohep tanoate (AP-7), dizocilpine maleate (MK-801), and gamma-glutamyl-amino methylsulfonic acid (GAMS). MR injections of the competitive (AP-7) an d non-competitive (MK-801) N-methyl-D-aspartic acid (NMDA) receptor an tagonists produced theta at short latencies (2.86 min; 4.02 min, respe ctively) and for long durations (116.1 min; 66.8 min, respectively). I t was further shown that the theta-eliciting effects of AP-7 injection s could be reliably and temporarily reversed with MR injections of NMD A. MR injections of the kainate/quisqualate receptor antagonist (GAMS) also produced theta at relatively short latencies (6.5 min) and for l ong durations (60.5 min) indicating that EAA effects on the MR are not NMDA receptor specific. Injections of each of the foregoing EAA antag onists into regions of the brainstem adjacent to the MR including the dorsal raphe nucleus and the medullary or pontine reticular formation generated theta at very long latencies or were without effect. The pre sent findings indicate EAA afferents to the MR normally exert an excit atory influence on the MR in its desynchronization of the hippocampal EEG, whereas the removal of EAA inputs to MR produces the opposite: a reduction of MR activity and hence the elicitation of theta. Thus, EAA afferents to the MR appear to play an important modulatory role in th e MR control of the hippocampal EEG.