sb-269970 and cyanopindolol

Previous studies have outlined an important role for serotonin (5-HT) in the development of synaptic connectivity and function in the cerebral cortex. In this study, we have examined the effects of 5-HT on synaptic function in prefrontal cortex at a time of intense synapse formation and remodelling. Whole-cell recordings in slices derived from animals aged postnatal (P) days 16-20 showed that administration of 5-HT induced a robust increase in synaptic activity that was blocked by CNQX but not by bicuculline. This 5-HT-induced increase in glutamate-mediated synaptic activity was pharmacologically heterogeneous as it was differentially inhibited by the receptor subtype-selective antagonists SB-269970, MDL 100907 and GR 113808 and thus involved 5-HT(7), 5-HT(2A) and 5-HT(4) receptors. These results, obtained in juvenile cortex, contrast with those seen in adults where the increase in spontaneous excitatory postsynaptic currents (sEPSCs) was mediated solely by 5-HT(2A) receptors. In developing cortex, activation of 5-HT(7), but not 5-HT(2A) or 5-HT(4) receptors, elicited a robust inward current. However, the facilitation of synaptic activity mediated by all three of these receptors involved increases in both the amplitude and frequency of sEPSCs and was blocked by TTX. These results are best interpreted as indicating that all three receptor subtypes increase synaptic activity by exciting neuronal elements within the slice. No evidence was found for a postsynaptic facilitation of synaptic currents by 5-HT. Together, these results show that the repertoire of electrophysiologically active 5-HT receptors in prefrontal cortex is developmentally regulated, and that 5-HT(7) and 5-HT(4) receptors play a previously unsuspected role in regulating synaptic activity in this region.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Amphetamines; Animals; Bicuculline; Fluorobenzenes; GABA-A Receptor Antagonists; Glutamic Acid; Indoles; Lidocaine; Male; Patch-Clamp Techniques; Phenols; Pindolol; Piperidines; Prefrontal Cortex; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptors, AMPA; Receptors, Metabotropic Glutamate; Receptors, Serotonin; Receptors, Serotonin, 5-HT4; Serotonin; Serotonin 5-HT1 Receptor Antagonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin 5-HT4 Receptor Antagonists; Serotonin Antagonists; Sodium Channel Blockers; Sulfonamides; Synapses; Tetrodotoxin; Time Factors