Serotonin reduces inhibition via 5-HT1A receptors in area CA1 of rat hippocampal slices in vitro.
We studied the effects of serotonin (5-HT) on intrinsic and synaptic responses of hippocampal CA1 cells. The effects were partially mimicked by the 5-HT1A receptor agonist, 8-OH-DPAT, and prevented by the 5-HT1A receptor antagonist, NAN-190. Polysynaptic fast and slow inhibitory postsynaptic potentials (IPSPs) were reduced in amplitude by 60-70% following application of both 5-HT and 8-OH-DPAT. Monosynaptic fast IPSPs were reduced by 60% and slow IPSPs by 90% following application of both drugs. Since there is a temporal overlap of fast and slow IPSPs, the reduction in fast IPSPs could have arisen indirectly from the larger effect of 5-HT on slow IPSPs. To overcome this problem we blocked the slow IPSPs with new, potent GABA-B antagonists, but still observed a similar reduction in the fast IPSP with 5-HT and 8-OH-DPAT. However, the reductions in the fast IPSPs could also have arisen from the 5-HT-induced total conductance increases. Using single-electrode voltage clamp and intracellular K+ channel blockers we still observed similar changes. 5-HT and 8-OH-DPAT had no effect upon GABA-A-mediated currents evoked by iontophoretic GABA application to the dendrites or the soma of CA1 pyramidal cells, Putative inhibitory internuerons were hyperpolarized by 5-HT and their evoked EPSPs strongly reduced by 5-HT and 8-OH-DPAT. Our data indicate that 5-HT modulates fast and slow synaptic inhibition of principal cells using presynaptic mechanisms involving the inhibition of inhibitory interneurons.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D004553:Electric Conductivity; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin