SEROTONIN DIFFERENTIALLY MODULATES RESPONSES MEDIATED BY SPECIFIC EXCITATORY AMINO-ACID RECEPTORS IN THE RAT LOCUS-CERULEUS

Microiontophoretic application of selective agonists for the three maj or excitatory amino acid receptors, N-methyl-D-aspartate (NMDA), quisq ualate and kainate, increased the discharge rate of noradrenergic locu s coeruleus (LC) neurons in vivo. NMDA activation was selectively atte nuated by iontophoretic application of 2-amino-5-phosphonopentanoate ( AP5), an antagonist at NMDA receptors, whereas kainate- and quisqualat e-evoked responses were attenuated by both NMDA and non-NMDA antagonis ts iontophoresis. NMDA- and quisqualate-evoked responses were signific antly decreased by co-iontophoresis of serotonin (5-HT). When the NMDA receptor-mediated component of the response to kainate was blocked wi th AP5 iontophoresis, 5-HT increased the response of LC neurons to kai nate. These results revealed that 5-HT differentially modulates the re sponsiveness of LC neurons to excitatory amino acids, depending on the receptor subtypes responsible for the neuronal activation.