Comparison of 5-hydroxytryptamine1A-mediated hyperpolarization in CA1 and CA3 hippocampal pyramidal cells.

5-hydroxytryptamine (5-HT) hyperpolarizes hippocampal pyramidal cells in both areas CA1 and CA3 through an increase in potassium conductance. The receptor mediating the hyperpolarization in CA1 has been characterized as the 5-HT1A receptor, but has not been identified in area CA3. Intracellular recording techniques were used to record from CA1 and CA3 pyramidal cells in a hippocampal slice preparation. 5-HT agonists and antagonists were applied in known concentrations by bath perfusion. Antagonists were tested alone and for their ability to block the hyperpolarization elicited by 5-HT. The 5-HT1 agonist 5-carboxyamidotryptamine and 5-HT were full agonists and the 5-HT1A-selective ligand 8-hydroxydipropyl-aminotetralin hydrobromide was a partial agonist in both CA3 and CA1. The rank order potency was 5-carboxyamidotryptamine > 8-hydroxydipropyl-aminotetralin hydrobromide > 5-HT for both regions. The agonists were a half-log unit less potent and the maximum response elicited by 5-carboxyamidotryptamine and 5-HT was greater in area CA3 than in area CA1. The selective 5-HT1A antagonist BMY 7378 and the 5-HT1A/2 antagonist spiperone were competitive in area CA1, but insurmountable in area CA3. Other 5-HT antagonists that were not effective in blocking the 5-HT-mediated hyperpolarization included ketanserin, odansetron and BRL 24924. Based on these results, we conclude that the hyperpolarization elicited by 5-HT in areas CA1 and CA3 is mediated by the 5-HT1A receptor. However, there are significant differences in the nature of the 5-HT1A receptor-mediated hyperpolarization that may be attributed to differences in receptor-effector number, receptor-effector coupling and/or the structure of the recognition site.