Effect of sub-chronic treatment with duloxetine on serotonin-2A receptor function in vivo and in vitro

A. Kagaya, H. Katagiri, Y. Tawara, A. Kugaya, M. Inagaki, I. Miyoshi, H. Jitsuiki, T. Kozuru, S. Kouhata, Y. Uchitomi, S. Morinobu, S. Yamawaki

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Abstract

We have investigated the effect of sub-chronic treatment with duloxetine on serotonin (5-HT)-2A receptor in rat brain and the receptor-mediated wet dog shake (WDS). The frequency of WDS, which is mediated by 5-HT-2A receptor stimulation, was significantly lower in rats treated with 20 mg/kg duloxetine for 7 days without the change in the density of 5-HT-2A receptor. The body weight increase was also lower in rats treated with 20 mg/kg duloxetine. Further, we have studied the effect of duloxetine on the receptor-mediated intracellular calcium (Ca2+) signaling using cultured rat glioma cells. In the study of cultured cells, pretreatment with duloxetine for 4 hr potently attenuated the subsequent Ca2+ increase in response to 5-HT without any direct antagonism against 5-HT-2A receptor. These results suggest that duloxetine may change the function of intracellular component distal from 5-HT-2A receptor, resulting in an inhibition of the subsequent Ca2+ rise in response to 5-HT and 5-HT-2A receptor-mediated behavior. These findings suggest the important role of 5-HT-2A receptor for the pathophysiology and treatment of mood disorders.

Original languageEnglish
Pages (from-to)541-554
Number of pages14
JournalBiogenic Amines
Volume16
Issue number6
Publication statusPublished - Dec 1 2001

Keywords

  • C6 glioma cells
  • Calcium
  • Duloxetine
  • Serotonin-2A receptor
  • Wet dog shake

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

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    Kagaya, A., Katagiri, H., Tawara, Y., Kugaya, A., Inagaki, M., Miyoshi, I., Jitsuiki, H., Kozuru, T., Kouhata, S., Uchitomi, Y., Morinobu, S., & Yamawaki, S. (2001). Effect of sub-chronic treatment with duloxetine on serotonin-2A receptor function in vivo and in vitro. Biogenic Amines, 16(6), 541-554.