Excitatory responses to serotonin (5-HT) in neurons of the rat piriform cortex: evidence for mediation by 5-HT1C receptors in pyramidal cells and 5-HT2 receptors in interneurons.
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 II and III 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 Ca(2+)-dependent outward currents with the characteristics of IM and IAHP. Pharmacological studies were designed to discriminate 5-HT2 from 5-HT1C 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-HT1C receptors, blocked the excitatory effect of 5-HT at lower concentrations in interneurons (IC50 = 31 nM) than in pyramidal cells (IC50 = 2.1 microM). Similarly, ritanserin, a drug which also has a higher affinity for 5-HT2 than 5-HT1C receptors, blocked the effect of 5-HT at lower concentrations in interneurons (IC50 = 400 nM) than in pyramidal cells (IC50 = 8.1 microM). In contrast, LY 53857, an antagonist with higher affinity for 5-HT1C 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-HT1C 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-HT1C receptors. In that both spiperone and ritanserin have higher affinity for 5-HT2 receptors than for 5-HT1C receptors and LY 53857 has a higher affinity for 5-HT1C receptors than for 5-HT2 receptors, these data suggest that in piriform cortex excitatory effects of 5-HT are mediated by 5-HT1C receptors in pyramidal cells an by 5-HT2 receptors in interneurons.
Sheldon
P W
PW
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut.
Aghajanian
G K
GK
D000818:Animals; D004594:Electrophysiology; D004873:Ergolines / Q000378:metabolism; D007395:Interneurons / Q000187:drug effects* / Q000502:physiology; D008032:Limbic System / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism / Q000502:physiology*; D016713:Ritanserin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
D004873:Ergolines; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; D012701:Serotonin; D013134:Spiperone; C032663:LY 53857; C015068:1-(3-chlorophenyl)piperazine