Functional interrelations between nucleus raphé dorsalis and nucleus raphé medianus: A dual probe microdialysis study of glutamate-stimulated serotonin release

Dual-probe in vivo microdialysis was used to explore the relationships between the two midbrain raphe nuclei, raphe dorsalis (DRN) and raphe medianus (MRN). Infusion of the excitatory neurotransmitter glutamate (10 mM) into the dorsal raphe nucleus produced a large increase in the extracellular 5-HT (5-HText) in the dorsal raphe (1400% of control values) that was limited to the time of infusion. This was followed by a significant decrease in extracellular 5-HT below baseline levels that continued for the duration of the experiment (3 h). Extracellular 5-HT (5-HText) was also increased to 500% of control values in the median raphe nucleus following infusion of 10 mM glutamate (GLU) into the dorsal raphe nucleus. Infusion of the competitive NMDA receptor antagonist AP5 prior to and during infusion of GLU into the DRN resulted in a decrease in the response to GLU in the DRN and an antagonism of the increase of 5-HText in the MRN. Infusion of 10 mM GLU into the lateral midbrain tegmentum, an area of the brain just lateral to the DRN, also increased 5-HText in the probe in the lateral midbrain tegmentum (900% of control) but did not alter 5-HText in the MRN. When glutamate was infused into the MRN, 5-HText was also increased to 1400% of control in a time course similar to that seen with infusion of GLU into the DRN. Infusion of glutamate into the MRN, however, did not alter the 5-HText in the DRN. These data suggest a serotonergic innervation of the median raphe nucleus by the dorsal raphe nucleus. A reciprocal innervation from the median raphe to the dorsal raphe is not mediated by glutamate, does not appear to be serotonergic, and does not regulate extracellular serotonin in the dorsal raphe.