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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

Serotonin 2C receptors tonically suppress the activity of mesocortical dopaminergic and... The present study evaluated, via a combined electrophysiological and dialysis 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 antagonist MDL100,907 failed to modify extracellular levels of dopamine (DA), noradrenaline (NA) or 5‐HT simultaneously quantified in single dialysate samples of freely‐moving rats, the 5‐HT2B/5‐HT2C antagonist SB206,553 dose‐dependently increased levels of DA and NA without affecting those of 5‐HT. This action was attributable to 5‐HT2C receptor blockade inasmuch as the selective 5‐HT2C antagonist SB242,084 likewise increased FCX levels of DA and NA, whereas the selective 5‐HT2B antagonist SB204,741 was ineffective. Further, the preferential 5‐HT2C receptor agonist Ro60‐0175 dose‐dependently depressed FCX levels of DA. The suppressive influence of 5‐HT2C receptors on DA release was also expressed on mesolimbic and nigrostriatal dopaminergic pathways, in that levels of DA in nucleus accumbens and striatum were likewise reduced by Ro60‐0175 and elevated, though less markedly, by SB206,553. In line with the above findings, Ro60‐0175 dose‐dependently decreased the firing rate of ventrotegmental dopaminergic and locus coeruleus (LC) adrenergic perikarya, whereas their activity was dose‐dependently enhanced by SB206,553. Furthermore, SB206,553 transformed the firing pattern of ventrotegmental dopaminergic 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 receptors exert a tonic, suppressive influence on the activity of mesocortical — as well as mesolimbic and nigrostriatal — dopaminergic pathways, likely via indirect actions expressed at the level of their cell bodies. Frontocortical adrenergic, but not serotonergic, transmission is also tonically suppressed by 5‐HT2C receptors. Synapse 36:205–221, 2000. © 2000 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Synapse Wiley

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

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References (106)

Publisher
Wiley
Copyright
Copyright © 2000 Wiley‐Liss, Inc.
ISSN
0887-4476
eISSN
1098-2396
DOI
10.1002/(SICI)1098-2396(20000601)36:3<205::AID-SYN5>3.0.CO;2-D
pmid
10819900
Publisher site
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Abstract

The present study evaluated, via a combined electrophysiological and dialysis 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 antagonist MDL100,907 failed to modify extracellular levels of dopamine (DA), noradrenaline (NA) or 5‐HT simultaneously quantified in single dialysate samples of freely‐moving rats, the 5‐HT2B/5‐HT2C antagonist SB206,553 dose‐dependently increased levels of DA and NA without affecting those of 5‐HT. This action was attributable to 5‐HT2C receptor blockade inasmuch as the selective 5‐HT2C antagonist SB242,084 likewise increased FCX levels of DA and NA, whereas the selective 5‐HT2B antagonist SB204,741 was ineffective. Further, the preferential 5‐HT2C receptor agonist Ro60‐0175 dose‐dependently depressed FCX levels of DA. The suppressive influence of 5‐HT2C receptors on DA release was also expressed on mesolimbic and nigrostriatal dopaminergic pathways, in that levels of DA in nucleus accumbens and striatum were likewise reduced by Ro60‐0175 and elevated, though less markedly, by SB206,553. In line with the above findings, Ro60‐0175 dose‐dependently decreased the firing rate of ventrotegmental dopaminergic and locus coeruleus (LC) adrenergic perikarya, whereas their activity was dose‐dependently enhanced by SB206,553. Furthermore, SB206,553 transformed the firing pattern of ventrotegmental dopaminergic 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 receptors exert a tonic, suppressive influence on the activity of mesocortical — as well as mesolimbic and nigrostriatal — dopaminergic pathways, likely via indirect actions expressed at the level of their cell bodies. Frontocortical adrenergic, but not serotonergic, transmission is also tonically suppressed by 5‐HT2C receptors. Synapse 36:205–221, 2000. © 2000 Wiley‐Liss, Inc.

Journal

Synapse – Wiley

Published: Jun 1, 2000

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