Dextromethorphan-induced psychotoxic behaviors cause sexual dysfunction in male mice via stimulation of σ-1 receptors

Yunsung Nam, Eun Joo Shin, Boo Keun Yang, Jae Hyung Bach, Ji Hoon Jeong, Yoon Hee Chung, Eon Sub Park, Zhengyi Li, Kee Won Kim, Young Bae Kwon, Toshitaka Nabeshima, Hyoung Chun Kim

研究成果: Article

14 引用 (Scopus)

抜粋

Dextromethorphan (DM) is a well-known antitussive dextrorotatory morphinan. We and others have demonstrated that sigma (σ) receptors may be important for DM-mediated neuromodulation. Because an earlier report suggested that DM might affect sexual function and that σ receptor ligands affect signaling pathways in the periphery, we examined whether DM-induced psychotoxic burden affected male reproductive function. We observed that DM had a high affinity at σ-1 receptors in the brain and testis but relatively low affinity at σ-2 receptors. Prolonged treatment with DM resulted in conditioned place preference and hyperlocomotion, followed by an increase in Fos-related antigen expression in the nucleus accumbens in male mice. Simultaneously, DM induced significant reductions in gonadotropin-releasing-hormone immunoreactivity in the hypothalamus. Moreover, we observed that DM induced increased sperm abnormalities and decreased sperm viability and sexual behavior. These phenomena were significantly attenuated by combined treatment with BD1047, a σ-1 receptor antagonist, but not by SM-21, a σ-2 receptor antagonist. Thus, these results suggest that DM psychotoxicity might lead to reproductive stress in male mice by activating σ-1 receptors.

元の言語English
ページ(範囲)913-922
ページ数10
ジャーナルNeurochemistry International
61
発行部数6
DOI
出版物ステータスPublished - 01-11-2012
外部発表Yes

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

これを引用

Nam, Y., Shin, E. J., Yang, B. K., Bach, J. H., Jeong, J. H., Chung, Y. H., Park, E. S., Li, Z., Kim, K. W., Kwon, Y. B., Nabeshima, T., & Kim, H. C. (2012). Dextromethorphan-induced psychotoxic behaviors cause sexual dysfunction in male mice via stimulation of σ-1 receptors. Neurochemistry International, 61(6), 913-922. https://doi.org/10.1016/j.neuint.2012.01.025