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Dextromethorphan-induced psychotoxic behaviors cause sexual dysfunction in male mice via stimulation

Dextromethorphan-induced psychotoxic behaviors cause sexual dysfunction in male mice via stimulation

  1. Behrang
    Neurochemistry International;Volume 61, Issue 6, November 2012, Pages 913–922
    Available online 2 February 2012

    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

    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.

    σ-1 Receptor; sigma-1 receptor
    Fos-related antigen
    Nucleus accumbens
    Gonadotropin-releasing hormone
    Sexual behavior