Action of serotonin in the medial prefrontal cortex: mediation by serotonin3-like receptors.
In the present study, we investigated the effects of various serotonin (5-HT) antagonists on 5-HT's action on medial prefrontal cortical cells (mPFc) using the techniques of single cell recording and microiontophoresis. The microiontophoretic application of 5-HT (10-80 nA) produced a current-dependent suppression of mPFc cell firing and this effect was blocked by the selective 5-HT3 receptor antagonists (+/-)-zacopride, ICS 205930 and granisetron at currents of 5-20 nA. Furthermore, the intravenous (i.v.) administration of (+/-)-zacopride (5-50 micrograms/kg) markedly attenuates the suppressive action of 5-HT on mPFc cell firing. In contrast, the microiontophoresis of 5-HT1 and 5-HT2 receptor antagonists such as (+/-)-pindolol, spiperone, metergoline, and ritanserin (10-20 nA) failed to block 5-HT's effect. In fact, in some cells, spiperone and ritanserin potentiated 5-HT's action and prolonged neuronal recovery. In addition, the intravenous administration of either ritanserin (5-2,000 micrograms/kg) or metergoline (4-2,400 micrograms/kg) failed to alter 5-HT's action. The electrical stimulation of the caudal linear raphe nucleus (CLi) suppressed the spontaneous activity of 83% of the mPFc cells tested by 45 +/- 2%. This suppression was significantly attenuated by the iontophoresis of granisetron (2.5-5 nA) but not by the 5-HT2 and 5-HT1C receptor antagonist ritanserin or the relatively selective 5-HT2 receptor antagonist (+)-MDL 11,939 (10-40 nA). However, the i.v. administration of ritanserin (0.5-1.5 mg/kg) or S-zacopride (0.1 mg/kg) significantly blocked the suppression of mPFc cell firing produced by CLi stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Ashby
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CR
Department of Psychiatry and Behavioral Sciences, State University of New York, Stony Brook 11794-8790.
Edwards
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E
Wang
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RY
D000704:Analysis of Variance; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D007478:Iontophoresis; D008297:Male; D008711:Metergoline / Q000008:administration & dosage / Q000494:pharmacology; D010869:Pindolol / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D016713:Ritanserin / Q000008:administration & dosage / Q000494:pharmacology; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013134:Spiperone / Q000008:administration & dosage / Q000494:pharmacology; D000077526:Tropisetron
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C066169:alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol; D016713:Ritanserin; D008711:Metergoline; D012701:Serotonin; D013134:Spiperone; D000077526:Tropisetron; C055971:zacopride; D010869:Pindolol