Serotonin Differentially Modulates Responses Mediated by Specific Excitatory Amino Acid Receptors in the Rat Locus Coeruleus

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Abstract
Microiontophoretic application of selective agonists for the three major excitatory amino acid receptors, N‐methyl‐d‐aspartate (NMDA), quisqualate and kainate, increased the discharge rate of noradrenergic locus coeruleus (LC) neurons in vivo. NMDA activation was selectively attenuated by iontophoretic application of 2‐amino‐5‐phosphonopentanoate (AP5), an antagonist at NMDA receptors, whereas kainate‐ and quisqualate‐evoked responses were attenuated by both NMDA and non‐NMDA antagonists iontophoresis. NMDA‐ and quisqualate‐evoked responses were significantly decreased by co‐iontophoresis of serotonin (5‐HT). When the NMDA receptor‐mediated component of the response to kainate was blocked with AP5 iontophoresis, 5‐HT increased the response of LC neurons to kainate. These results revealed that 5‐HT differentially modulates the responsiveness of LC neurons to excitatory amino acids, depending on the receptor subtypes responsible for the neuronal activation.