In vivo actions of the selective 5-HT1A receptor agonist BAY x 3702 on serotonergic cell firing and release

We investigated the effects of the novel 5-HT1A receptor agonist BAY x 3702 on the serotonergic function in rat brain using single unit recordings in the dorsal raphe nucleus (DR) of anesthetized rats and in vivo microdialysi s in freely moving rats. The administration of BAY x 3702 (0.25-4 mu g/kg i .v.) suppressed the firing activity of 5-HT neurones. This effect was antag onized by a low dose of the selective 5-HT1A receptor antagonist WAY 100635 (5 mu g/kg i.v.). In microdialysis experiments, BAY x 3702 (10-100 mu g/kg s.c.) reduced dose -dependently the 5-HT output in the dorsal and median raphe (MnR) nucleus, dorsal hippocampus (DHPC) and medial prefrontal cortex (mPFC) in a regional ly selective manner. Maximal effects were observed in the MnR and mPFC, wit h reductions to similar to 15% of baseline at a dose of 0.1 mg/kg s.c. The decrease in 5-HT output produced in the DR and DHPC was more moderate, to 4 5% of baseline at 0.1 mg/kg s.c. BAY x 3702. WAY 100635 (0.3 mg/kg s.c.) co mpletely antagonized the effect of BAY x 3702 (30 mu g/kg s.c.). The applic ation of BAY x 3702 in the DR (1-100 mu M) reduced the local 5-HT output to 25% of baseline. In rats implanted with two dialysis probes (in DR and mPF C) the application of BAY x 3702 (30 mu M) in the DR reduced the 5-HT outpu t in the DR and that in mPFC. These effects were significantly antagonized by the co-perfusion of WAY 100635 (100 mu M) in the DR. Overall, these results indicate that the systemic administration of BAY x 3 702 reduces the 5-HT release with high potency through the activation of mi dbrain 5-HT1A receptors.