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Action of serotonin in the medial prefrontal cortex: Mediation by serotonin 3 ‐like receptors
Author(s) -
Ashby Charles R.,
Edwards Emmeline,
Wang Rex Y.
Publication year - 1992
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890100103
Subject(s) - serotonin , prefrontal cortex , neuroscience , mediation , action (physics) , 5 ht receptor , psychology , receptor , medicine , cognition , physics , political science , quantum mechanics , law
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 microintophoretic 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‐HT 3 receptor antagonists (±)‐zacopride, ICS 205930 and granisetron at currents of 5–20 nA. Furthermore, the intravenous (i.v.) administration of (±)‐zacopride (5–50 μg/kg) markedly attenuates the suppressive action of 5‐HT on mPFc cell firing. In contrast, the microinotophoresis of 5‐HT 1 and 5‐HT 2 receptor antgonists 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 μg/kg) or metergoline (4–2,400 μg/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‐HT 2 and 5‐HT 1C receptor antagonist ritanserin or the relatively selective 5‐HT 2 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. Overall, our results suggest that 5‐HT's physiological effect in the mPFc may be primarily mediated by its interaction with 5‐HT 3 ‐like receptors and that ritanserin's blockade of CLi‐induced suppression of mPFc cell firing may be indirect.