Physiological effects of selective 5-HT1a and 5-HT1b ligands in rat hippocampus: comparison to 5-HT.

The responses of CA1 neurons to topical application of serotonin (5-HT) and selective 5-HT1a and 5-HT1b agonists were examined with intracellular recording in the hippocampal slice. 5-HT produced a uniform hyperpolarizing response associated with an increase in K conductance as previously reported. In addition a marked reduction was recorded in slow afterhyperpolarization (AHP) which follows a burst discharge. 8-OH-DPAT, ipsapirone and LY165,163 partially mimicked the hyperpolarizing response to 5-HT when first applied to the slice. However, these 5-HT1a ligands antagonized responses to subsequent applications of 5-HT. Topical application of the 5-HT1b ligand TFMPP on the slice did not produce the direct or antagonistic action seen with the 5-HT1a ligands. It is suggested that the physiological response to 5-HT in the rat hippocampus is mediated by a 5-HT1a receptor. The currently available 5-HT1a ligands show a low agonist potential and a high antagonist action towards the responses of hippocampal neurons to 5-HT. Definite classification of the hyperpolarizing response to 5-HT awaits development of more specific ligands having a pure agonistic activity.