EN
BACKGROUND AND AIMS: The 5-HT7 receptor is one of the several 5-HT receptor subtypes which are expressed in DRN neurons. Some previous findings suggested that 5-HT7 receptors in the DRN are localized on local GABAergic interneurons, which modulate the activity of 5-HT projection neurons. The aims of this study were to determine how the 5-HT7 receptor activation and blockade influence the GABAergic synaptic input to presumed 5-HT DRN neurons and whether blockade of the 5-HT7 receptor would affect the release and metabolism of 5-HT in the prefrontal cortex in vivo. METHODS: Male Wistar rats, with microdialysis probes implanted in the PFC, received ip injections of 5-HT7 receptor antagonist, SB 269970. 5-HT and 5-HIAA, were analyzed by HPLC. In another set of experiments whole-cell recordings were carried out from DRN slices. SB 269970 was used to block the 5-HT7 receptor. To activate the 5-HT7 receptor 5-CT was applied in the presence of WAY 100635. RESULTS: Ip administration of SB269970 induced an increase in the level of 5-HT and 5-HIAA in PFC. SB 269970 application resulted in a depolarization of presumed DRN projection neurons and in an increase in the spontaneous firing frequency. A hyperpolarization of the cells and a decrease in the spontaneous firing frequency were observed after activation of the 5-HT7 receptor. Blockade of the 5-HT7 receptor caused a decrease in the mean frequency of sIPSCs, while its activation induced an increase. CONCLUSIONS: These results show that blockade of the 5-HT7 receptor enhances the release and metabolism of 5-HT in the PFC. This effect appears to be mediated by depolarization and enhanced firing of DRN serotonergic neurons resulting from a decreased inhibitory synaptic input received by the projection cells. Activation of the 5-HT7 receptor caused opposite effects on activity and the inhibitory input to putative DRN projection neurons. Support: National Science Centre Poland grant DEC-2013/11/B/ NZ4/04743.