Nitric oxide modulates N-methyl-D-aspartate-evoked serotonin release in the raphe nuclei and frontal cortex of the freely moving rat.

The role of nitric oxide (NO) in N-methyl-D-aspartate (NMDA)-regulated release of 5-hydroxytryptamine (5-HT) in the frontal cortex and raphe nuclei of freely moving rats has been studied using microdialysis with dual probes, one in each region of the same animal. In order to do this the selective neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI; 1 mM) and the NO donor S-nitroso-N-penicillamine (SNAP; 500 microM-5 mM) were used. All drugs were infused into the raphe via the dialysis probe. NMDA showed an inverse concentration effect on 5-HT release in the raphe with 25 microM decreasing 5-HT release and 100 microM increasing release. At the same time the converse effect was seen in the frontal cortex. Co-infusion of 7-NI abolished the effect of 100 microM but not 25 microM NMDA. 7-NI given alone decreased raphe 5-HT release with a concomitant increase being seen in the frontal cortex. Low concentrations of SNAP infused into the raphe were found to decrease 5HT release locally but increase release in the frontal cortex. In contrast the highest concentration of SNAP used was found to have the opposite effect in both brain regions. These data suggest that NO plays a role in mediating both basal and NMDA-evoked changes in serotonergic transmission between the raphe and frontal cortex.