Serotonin(2C) receptors tonically suppress the activity of mesocortical dopaminergic and adrenergic, but not serotonergic, pathways: A combined dialysis and electrophysiological analysis in the rat

The present study evaluated, via a combined electrophysiological and dialys is approach, the potential influence of serotonin (5-HT)(2C) as compared to 5-HT2A and 5-HT2B receptors on dopaminergic, adrenergic, and serotonergic transmission in frontal cortex (FCX). Whereas the selective 5-HT2A antagoni st MDL100,907 failed to modify extracellular levels of dopamine (DA), norad renaline (NA) or 5-HT simultaneously quantified in single dialysate samples of freely-moving rats, the 5-HT2B/5-HT2C antagonist SB206,553 dose-depende ntly increased levels of DA and NA without affecting those of 5-HT. This ac tion was attributable to 5-HT2C receptor blockade inasmuch as the selective 5-HT2C antagonist SB242,084 likewise increased FCX levels of DA and NA, wh ereas the selective 5-HT2B antagonist SB204,741 was ineffective. Further, t he preferential 5-HT2C receptor agonist Ro60-0175 dose-dependently depresse d FCX levels of DA. The suppressive influence of 5-HT2B receptors on DA rel ease was also expressed on mesolimbic and nigrostriatal dopaminergic pathwa ys, in that levels of DA in nucleus accumbens and striatum were likewise re duced by Ro60-0175 and elevated, though less markedly, by SB206,553. In Lin e with the above findings, Ro60-0175 dose-dependently decreased the firing rate of ventrotegmental dopaminergic and locus coeruleus (LC) adrenergic pe rikarya, whereas their activity was dose-dependently enhanced by SB206,553. Furthermore, SB206,553 transformed the firing pattern of ventrotegmental d opaminergic neurons into a burst mode. In contrast to SB206,553, MDL100,907 had little affect on the firing rate of dopaminergic or adrenergic neurons . In conclusion, as compared to 5-HT2A and 5-HT2B receptors, 5-HT2C recepto rs exert a tonic, suppressive influence on the activity of mesocortical - a s well as mesolimbic and nigrostriatal dopaminergic pathways, likely via in direct actions expressed at the level of their cell bodies. Frontocortical adrenergic, but not serotonergic, transmission is also tonically suppressed by 5-HT2C receptors. (C) 2000 Wiley-Liss, Inc.