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

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Abstract

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.

Original languageEnglish
Pages (from-to)913-922
Number of pages10
JournalNeurochemistry International
Volume61
Issue number6
DOIs
Publication statusPublished - 01-11-2012

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All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

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