Pharmacological Evidence for 5-HT6 Receptor Modulation of 5-HT Neuron Firing in Vivo

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• 作者：Julia T. Brouard ; Judith V. Schweimer ; Rachel Houlton ; Katherine E. Burnham ; Philip Qu茅r茅e ; Trevor Sharp
• 刊名：ACS Chemical Neuroscience
• 出版年：2015
• 出版时间：July 15, 2015
• 年：2015
• 卷：6
• 期：7
• 页码：1241-1247
• 全文大小：319K
• ISSN：1948-7193

文摘

5-Hydroxytryptamine (5-HT) neurons in the midbrain dorsal raphe nucleus (DRN) are implicated in the drug treatment and pathophysiology of a wide variety of neuropsychiatric disorders. Accumulating evidence suggests that 5-HT₆ receptors may be located and functional in the DRN; therefore, 5-HT₆ receptor ligands may have potential as novel modulators of 5-HT neurotransmission. The current study investigated the effect of intravenous (i.v.) administration of the selective 5-HT₆ receptor agonist, WAY-181187, and antagonist, SB-399885, on the firing of 5-HT neurons in the DRN in vivo. Extracellular recordings were made in the DRN of anesthetized rats, and single 5-HT neurons were identified on the basis of electrophysiological properties combined with juxtacellular labeling and postmortem immunohistochemical analysis. WAY-181187 (1鈥? mg/kg i.v.) caused a dose-dependent increase in 5-HT neuron firing rate. In comparison, SB-399885 (0.125鈥? mg/kg i.v.) caused a dose-dependent decrease in 5-HT neuron firing rate, an effect reversed by WAY-181187 (3 mg/kg i.v.). These effects of WAY-181187 and SB-399885 were observed in two separate sets of experiments. In summary, the current data show the modulation of 5-HT neuronal firing by the 5-HT₆ ligands WAY-181187 and SB-399885 and are consistent with the presence of 5-HT₆ receptor-mediated positive feedback control of 5-HT neurons.