Abstract

The present studies evaluated the effects of acute and long-term administration of the 5-HT_1A agonist BAY x 3702 on the responsiveness of dorsal raphe 5-HT neurons and of dorsal hippocampus CA₃ pyramidal neurons. BAY x 3702 potently reduced the firing activity of 5-HT neurons and of CA₃ pyramidal neurons when applied by microiontophoresis and this inhibitory effect of BAY x 3702 was fully antagonized by low intravenous doses of the 5-HT_1A antagonist WAY 100635. Concurrent microiontophoretic application of BAY x 3702 did not antagonize the suppressant effect of 5-HT on firing activity of 5-HT and CA₃ pyramidal neurons. Sustained administration of BAY x 3702 for 2 days (1 and 1.25 mg/kg/day using osmotic minipumps implanted subcutaneously) markedly decreased the firing rate of dorsal raphe 5-HT neurons. This was followed by a full recovery to normal after only 7 days of treatment. The postsynaptic 5-HT_1A receptors in the hippocampus, contrary to the presynaptic 5-HT_1A receptors, were not desensitized after a 14-day treatment. In conclusion, BAY x 3702 acted as a full and potent agonist both at somatodendritic 5-HT_1A autoreceptors and at postsynaptic 5-HT_1A receptors. Long-term administration of BAY x 3702 resulted in a desensitization of the somatodendritic 5-HT_1A autoreceptors, but in an unaltered responsiveness of 5-HT_1A receptors on pyramidal neurons. These results suggest that sustained administration of BAY x 3702 enhances neurotransmission at postsynaptic 5-HT_1Areceptors.