As a prerequisite to pharmacological analysis of the excitatory effects of serotonin (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 I1 and 111 are 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 IM and Imp.
Pharmacological studies were designed to discriminate 5-HT2 from 5-HTlc 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-HTlc receptors, blocked the excitatory effect of 5-HT at lower concentrations in interneurons (ICs0 = 31 nM) than in pyramidal cells = 2.1 pM). Similarly, ritanserin, a drug which also has a higher affinity for 5-HT2 than 5-HTlc receptors, blocked the effect of 5-HT at lower concentrations in interneurons (IC50 = 400 nM) than in pyramidal cells (ICs0 = 8.1 pM). In contrast, LY 53857, an antagonist with higher affinity for 5-HTlc than for 5-HT, receptors, blocked the effect of 5-HT at lower concentrations in pyramidal cells (IC,, = 26 nM) than in interneurons (IC50 = 364 nM). The 5-HTIc 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-HTIc receptors.
In that both spiperone and ritanserin have higher affinity for 5-HT2 receptors than for 5-HTlc receptors and LY 53857 has a higher affinity for 5-HTlc receptors than for 5-HT2 receptors, these data suggest that in piriform cortex excitatory effects of 5-HT are mediated by 5-HTIc receptors in pyramidal cells and by 5-HT2 receptors in interneurons.