Excitation of interneurons in piriform cortex by 5-hydroxytryptamine: blockade by MDL 100,907, a highly selective 5-HT2A receptor antagonist.
Electrophysiological studies have suggested that a subpopulation of interneurons near the border of layer II and III in rat piriform cortex are excited by serotonin (5-hydroxytryptamine; 5-HT) via 5-HT2A (formerly 5-HT2) rather than 5-HT2C (formerly 5-HT1C) receptors. However, the pharmacological agents used in those studies were limited in specificity. In the present study, we tested a new, highly selective 5-HT2A receptor antagonist MDL 100,907 (R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl-ethyl)]-4- piperidine-methanol, which has a 300-fold greater affinity for 5-HT2A than 5-HT1C receptors or alpha 1-adrenoceptors) on excitatory responses of interneurons to 5-HT in rat piriform cortex slices. We observed a parallel, reversible rightward shift in the 5-HT concentration-response curve in the presence of 1-10 nM concentrations of MDL 100,907. Schild regression analysis resulted in a slope of 1.13 and a Kd value of 1.17 which is close to the published Ki value of 0.36 for MDL 100,907. These data confirm that 5-HT2A rather than 5-HT2C receptors mediate excitation by 5-HT of interneurons in the piriform cortex. Because of its rapid equilibration and reversibility, MDL 100,907 appears to be an excellent tool for studies of 5-HT2A receptor function in the brain.
Marek
G J
GJ
Department of Psychiatry, Yale University School of Medicine, Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven 06508.
Aghajanian
G K
GK
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005464:Fluorobenzenes / Q000494:pharmacology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009833:Olfactory Pathways / Q000187:drug effects* / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D005464:Fluorobenzenes; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; D012701:Serotonin; C079049:volinanserin