Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons.
In low cerveau isolé transected rats, the effects of microiontophoretic application of putative serotonin 5-HT1A and 5-HT1B agonists on the spontaneous firing rate of CA1 pyramidal cells were compared to those of 5-HT. In contrast to the large current-dependent suppression of unit activity observed with 5-HT, the 5-HT1A compounds, ipsapirone, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and LY 165163 (p-aminophenylethyl-m-trifluoromethylphenylpiperazine) and the 5-HT1B compounds, mCPP (m-chlorophenylpiperazine) and TFMPP (trifluoromethylphenylpiperazine), produced only weak inhibition of spontaneous firing. Conversely, using identical ejection parameters, ipsapirone and LY 165163 (previously reported) and 8-OH-DPAT were as effective as 5-HT in inhibiting markedly the baseline activity of serotonergic dorsal raphe neurons; mCPP and TFMPP (previously reported) were only weakly active. In view of the minor suppressant effects of the 5-HT1A agonists on the firing of pyramidal cells, a modulatory role for these compounds was sought. Excitation of pyrimadal cells, induced by microiontophoretic application of glutamate, was attenuated by ipsapirone and 8-OH-DPAT; however, when directly compared in the same cells, ipsapirone was no more effective than the 5-HT1B agonist, mCPP. In summary, the inability of CA1 pyramidal cells to distinguish the actions of 5-HT1A and 5-HT1B ligands is in sharp contrast to the striking differences observed for these compounds with dorsal raphe neurons. Consistent with these findings is the idea that 5-HT1A compounds are full agonists on dorsal raphe neurons but only partial agonists on pyramidal cells.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C044643:LY 165163