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 language | English |
|---|---|
| Pages (from-to) | 913-922 |
| Number of pages | 10 |
| Journal | Neurochemistry International |
| Volume | 61 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 01-11-2012 |
| Externally published | Yes |
Fingerprint
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
- Cell Biology
Cite this
}
Dextromethorphan-induced psychotoxic behaviors cause sexual dysfunction in male mice via stimulation of σ-1 receptors. / Nam, Yunsung; Shin, Eun Joo; Yang, Boo Keun; Bach, Jae Hyung; Jeong, Ji Hoon; Chung, Yoon Hee; Park, Eon Sub; Li, Zhengyi; Kim, Kee Won; Kwon, Young Bae; Nabeshima, Toshitaka; Kim, Hyoung Chun.
In: Neurochemistry International, Vol. 61, No. 6, 01.11.2012, p. 913-922.Research output: Contribution to journal › Article
TY - JOUR
T1 - Dextromethorphan-induced psychotoxic behaviors cause sexual dysfunction in male mice via stimulation of σ-1 receptors
AU - Nam, Yunsung
AU - Shin, Eun Joo
AU - Yang, Boo Keun
AU - Bach, Jae Hyung
AU - Jeong, Ji Hoon
AU - Chung, Yoon Hee
AU - Park, Eon Sub
AU - Li, Zhengyi
AU - Kim, Kee Won
AU - Kwon, Young Bae
AU - Nabeshima, Toshitaka
AU - Kim, Hyoung Chun
PY - 2012/11/1
Y1 - 2012/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84868203861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868203861&partnerID=8YFLogxK
U2 - 10.1016/j.neuint.2012.01.025
DO - 10.1016/j.neuint.2012.01.025
M3 - Article
C2 - 22326744
AN - SCOPUS:84868203861
VL - 61
SP - 913
EP - 922
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
IS - 6
ER -