PT - JOURNAL ARTICLE AU - Jianming Dong AU - Claude de Montigny AU - Pierre Blier TI - Full Agonistic Properties of Bay x 3702 on Presynaptic and Postsynaptic 5-HT<sub>1A</sub> Receptors Electrophysiological Studies in the Rat Hippocampus and Dorsal Raphe. DP - 1998 Sep 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1239--1247 VI - 286 IP - 3 4099 - http://jpet.aspetjournals.org/content/286/3/1239.short 4100 - http://jpet.aspetjournals.org/content/286/3/1239.full SO - J Pharmacol Exp Ther1998 Sep 01; 286 AB - The present studies evaluated the effects of acute and long-term administration of the 5-HT1A 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-HT1A 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-HT1A receptors in the hippocampus, contrary to the presynaptic 5-HT1A 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-HT1A autoreceptors and at postsynaptic 5-HT1A receptors. Long-term administration of BAY x 3702 resulted in a desensitization of the somatodendritic 5-HT1A autoreceptors, but in an unaltered responsiveness of 5-HT1A receptors on pyramidal neurons. These results suggest that sustained administration of BAY x 3702 enhances neurotransmission at postsynaptic 5-HT1Areceptors. The American Society for Pharmacology and Experimental Therapeutics