Excitatory responses to serotonin (5‐HT) in neurons of the rat piriform cortex: Evidence for mediation by 5‐HT_1C receptors in pyramidal cells and 5‐HT₂ receptors in interneurons

As a prerequisite to pharmacological analysis of the excitatory effects of serotoinin (5‐HT) on piriform pyramidal cells and interneurons, this study first examined the physiological characteristics of these two cell types. Intracellular recordings confirmed that the subpopulation of 5‐HT‐activated cells located at the border of layers II and III and indeed interneurons. Voltage clamp recordings in pyramidal cells showed that the increase in excitability produced by 5‐HT in these cells was the result of voltage‐ and Ca²⁺‐dependent outward currents with the characteristics of I_M and I_AHP.

Pharmacological studies were designed to discriminate 5‐HT₂ from 5‐HT_1C responses in interneurons and pyramidal cells of piriform cortex. The 5‐HT antagonist spiperone, which has a much higher affinity for 5‐HT₂ receptors than for 5‐HT_1C receptors, blocked the excitatory effect of 5‐HT at lower concentrations in interneurons (IC₅₀ = 31 nM) than in pyramidal cells (IC₅₀ = 2.1 μM). Similarly, ritanserin, a drug which also has a higher affinity for 5‐HT₂ than 5‐HT_1C receptors, blocked the effect of 5‐HT at lower concentrations in interneurons (IC₅₀ = 400 nM) than in pyramidal cells (IC₅₀ = 8.1 μM). In contrast, LY 53857, an antagonist with higher affinity for 5‐HT_1C than for 5‐HT₂ receptors, blocked the effect of 5‐HT at lower concentrations in pyramidal cells (IC₅₀ = 26 nM) than in interneurons (IC₅₀ = 364 nM). The 5‐HT_1C partial agonist/5‐HT₂ antagonist mCPP produced agonist‐like effects in only 66% of pyramidal cells tested indicating that not all pyramidal cells may express 5‐HT_1C receptors.

In that both spiperone and ritanserin have higher affinity for 5‐HT₂ receptors than for 5‐HT_1C receptors and LY 53857 has a higher affinity for 5‐HT_1C receptors than for 5‐HT₂ receptors, these data suggest that in piriform cortex excitatory effects of 5‐HT are mediated by 5‐HT_1C receptors in pyramidal cells and by 5‐HT₂ receptors in interneurons.