Self-Exposure to the Male Pheromone ESP1 Enhances Male Aggressiveness in Mice

• Published in: Current biology 2016-05, Vol.26 (9), p.1229-1234
• Main Authors: Hattori, Tatsuya, Osakada, Takuya, Matsumoto, Ayaka, Matsuo, Naoki, Haga-Yamanaka, Sachiko, Nishida, Takaya, Mori, Yuji, Mogi, Kazutaka, Touhara, Kazushige, Kikusui, Takefumi
• Format: Article
• Language: English
• Subjects: Aggression - drug effects; Animals; Gene Expression Regulation - drug effects; Genes, fos - genetics; Genes, fos - physiology; Male; Mice; Proteins - metabolism; Proteins - pharmacology; Tears - chemistry
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2016.03.029

Exocrine gland-secreting peptide 1 (ESP1) released into male tear fluids is a male pheromone that stimulates sexually receptive behavior in female mice via the vomeronasal sensory system. ESP1 also induces c-Fos expression in male brain regions distinct from those in females. However, behavior in males following ESP1 exposure has not been examined. In the present study, we show that ESP1, in conjunction with unfamiliar male urine, enhances male aggression via the specific vomeronasal receptor V2Rp5. In addition, male mice that secrete ESP1 but lack V2Rp5 exhibit a lower level of aggressiveness than do mice that express V2Rp5. These results suggest that ESP1 not only acts as a male pheromone in both sexes but also serves as an auto-stimulatory factor that enhances male aggressiveness by self-exposure. Finally, re-activation of ESP1-induced c-Fos-positive neurons by using the designer receptor exclusively activated by designer drug (DREADD) approach resulted in enhancement of sexual and aggressive behaviors in female and male mice, respectively, indicating that sexually dimorphic activation in the brain is a neural basis for the sex-specific behavioral responses to ESP1. •ESP1 in male mouse tears enhances aggression in recipients in conjunction with urine•Self-secreted ESP1 auto-stimulates aggressiveness in males•Reactivation of ESP1-induced c-Fos in neurons by DREADDs was sexually dimorphic•The reactivation by DREADDs reproduced the sex-specific behavioral response to ESP1 Sexual cues directly trigger ritualistic behavioral sequences mediated by pre-programmed neural circuits. Hattori et al. demonstrate that male mouse pheromone ESP1 stimulates male aggression and female sexual behavior via sex-specific neural activation. ESP1 also acts as an auto-stimulatory factor enhancing aggression through self-exposure.