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

• Published in: Synapse (New York, N.Y.) N.Y.), 2000-06, Vol.36 (3), p.205-221
• Main Authors: Gobert, A, Rivet, J M, Lejeune, F, Newman-Tancredi, A, Adhumeau-Auclair, A, Nicolas, J P, Cistarelli, L, Melon, C, Millan, M J
• Format: Article
• Language: English
• Subjects: Animals; Cerebral Cortex - physiology; Corpus Striatum - metabolism; Dialysis; Dopamine - metabolism; Dopamine - physiology; Electrophysiology; Epinephrine - metabolism; Epinephrine - physiology; Extracellular Space - metabolism; Frontal Lobe - metabolism; Locus Coeruleus - cytology; Locus Coeruleus - physiology; Male; Neurons - physiology; Nucleus Accumbens - metabolism; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2B; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin - metabolism; Receptors, Serotonin - physiology; Serotonin - metabolism; Serotonin - physiology; Tegmentum Mesencephali - cytology; Tegmentum Mesencephali - metabolism
• ISSN: 0887-4476
• DOI: 10.1002/(SICI)1098-2396(20000601)36:3<205::AID-SYN5>3.0.CO;2-D

The present study evaluated, via a combined electrophysiological and dialysis approach, the potential influence of serotonin (5-HT)(2C) as compared to 5-HT(2A) and 5-HT(2B) receptors on dopaminergic, adrenergic, and serotonergic transmission in frontal cortex (FCX). Whereas the selective 5-HT(2A) 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-HT(2B)/5-HT(2C) antagonist SB206,553 dose-dependently increased levels of DA and NA without affecting those of 5-HT. This action was attributable to 5-HT(2C) receptor blockade inasmuch as the selective 5-HT(2C) antagonist SB242,084 likewise increased FCX levels of DA and NA, whereas the selective 5-HT(2B) antagonist SB204,741 was ineffective. Further, the preferential 5-HT(2C) receptor agonist Ro60-0175 dose-dependently depressed FCX levels of DA. The suppressive influence of 5-HT(2C) 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-HT(2A) and 5-HT(2B) receptors, 5-HT(2C) 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-HT(2C) receptors.