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Risperidone stimulates food intake and induces body weight gain via the hypothalamic arcuate nucleus 5-HT2c receptor—NPY pathway

Journal Article


Abstract


  • © 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd. Aims: Many patients taking risperidone for the treatment of psychiatric disorders experience substantial body weight gain. Researchers have speculated that risperidone induces obesity by modulating central signals; however, the precise central mechanisms involved remain to be fully elucidated. Methods: Twenty-four C57BL/6J mice were divided into four groups: a control group; a risperidone-treated group; a lorcaserin-treated group; and a combined risperidone + lorcaserin-treated group. The mice were received the corresponding treatments for 4 weeks, and their brains were collected for in situ hybridization analysis. A subset of C57BL/6J mice was administrated with risperidone or placebo, and brains were collected 60 minutes post-treatment for determination of c-fos activity. In addition, brains of NPY-GFP mice treated with or without risperidone were collected to perform colocalization of NPY and c-fos, as well as NPY and 5-HT2c receptor using immunohistochemistry. Results: There was significantly elevated c-fos expression in the hypothalamic arcuate nucleus (Arc) of risperidone-treated mice. More than 68% c-fos-positive neurons were NPY-expressing neurons. Furthermore, in situ hybridization revealed that Arc NPY mRNA expression was significantly increased in the risperidone-treated group compared with control group. Moreover, we identified that 95% 5-HT2c receptors were colocalized with NPY positive neurons, and increased Arc NPY mRNA expression induced by risperidone was markedly reduced by cotreatment with lorcaserin, a specific 5-HT2c receptor agonist. Conclusion: Our findings provide critical insight into the mechanisms underlying antipsychotic-induced obesity, which may assist the development of therapeutic strategies to address metabolic side effects of risperidone.

Authors


  •   Wan, Xiao (external author)
  •   Zeng, Fan (external author)
  •   Huang, Xu-Feng
  •   Yang, He (external author)
  •   Wang, Lan (external author)
  •   Shi, Yan-Chuan (external author)
  •   Zhang, Zhi (external author)
  •   Lin, Shu (external author)

Publication Date


  • 2019

Citation


  • Wan, X., Zeng, F., Huang, X., Yang, H., Wang, L., Shi, Y., Zhang, Z. & Lin, S. (2019). Risperidone stimulates food intake and induces body weight gain via the hypothalamic arcuate nucleus 5-HT2c receptor—NPY pathway. CNS Neuroscience and Therapeutics, 1-9.

Scopus Eid


  • 2-s2.0-85077163190

Number Of Pages


  • 8

Start Page


  • 1

End Page


  • 9

Place Of Publication


  • United Kingdom

Abstract


  • © 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd. Aims: Many patients taking risperidone for the treatment of psychiatric disorders experience substantial body weight gain. Researchers have speculated that risperidone induces obesity by modulating central signals; however, the precise central mechanisms involved remain to be fully elucidated. Methods: Twenty-four C57BL/6J mice were divided into four groups: a control group; a risperidone-treated group; a lorcaserin-treated group; and a combined risperidone + lorcaserin-treated group. The mice were received the corresponding treatments for 4 weeks, and their brains were collected for in situ hybridization analysis. A subset of C57BL/6J mice was administrated with risperidone or placebo, and brains were collected 60 minutes post-treatment for determination of c-fos activity. In addition, brains of NPY-GFP mice treated with or without risperidone were collected to perform colocalization of NPY and c-fos, as well as NPY and 5-HT2c receptor using immunohistochemistry. Results: There was significantly elevated c-fos expression in the hypothalamic arcuate nucleus (Arc) of risperidone-treated mice. More than 68% c-fos-positive neurons were NPY-expressing neurons. Furthermore, in situ hybridization revealed that Arc NPY mRNA expression was significantly increased in the risperidone-treated group compared with control group. Moreover, we identified that 95% 5-HT2c receptors were colocalized with NPY positive neurons, and increased Arc NPY mRNA expression induced by risperidone was markedly reduced by cotreatment with lorcaserin, a specific 5-HT2c receptor agonist. Conclusion: Our findings provide critical insight into the mechanisms underlying antipsychotic-induced obesity, which may assist the development of therapeutic strategies to address metabolic side effects of risperidone.

Authors


  •   Wan, Xiao (external author)
  •   Zeng, Fan (external author)
  •   Huang, Xu-Feng
  •   Yang, He (external author)
  •   Wang, Lan (external author)
  •   Shi, Yan-Chuan (external author)
  •   Zhang, Zhi (external author)
  •   Lin, Shu (external author)

Publication Date


  • 2019

Citation


  • Wan, X., Zeng, F., Huang, X., Yang, H., Wang, L., Shi, Y., Zhang, Z. & Lin, S. (2019). Risperidone stimulates food intake and induces body weight gain via the hypothalamic arcuate nucleus 5-HT2c receptor—NPY pathway. CNS Neuroscience and Therapeutics, 1-9.

Scopus Eid


  • 2-s2.0-85077163190

Number Of Pages


  • 8

Start Page


  • 1

End Page


  • 9

Place Of Publication


  • United Kingdom