title: Self-Exposure to the Male Pheromone ESP1 Enhances Male Aggressiveness in Mice.
abstract: 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.
authors.affiliation: Companion Animal Research, School of Veterinary Medicine, Azabu University, Sagamihara 252-5201, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan; ERATO Touhara Chemosensory Signal Project, JST, University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Osakada
authors.affiliation: Companion Animal Research, School of Veterinary Medicine, Azabu University, Sagamihara 252-5201, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Molecular and Behavioral Neuroscience, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsuo
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Haga-Yamanaka
authors.affiliation: Laboratory of Veterinary Ethology, University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Nishida
authors.affiliation: Laboratory of Veterinary Ethology, University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Companion Animal Research, School of Veterinary Medicine, Azabu University, Sagamihara 252-5201, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Mogi
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan; ERATO Touhara Chemosensory Signal Project, JST, University of Tokyo, Tokyo 113-8657, Japan. Electronic address: ktouhara@mail.ecc.u-tokyo.ac.jp.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Touhara
authors.affiliation: Companion Animal Research, School of Veterinary Medicine, Azabu University, Sagamihara 252-5201, Japan. Electronic address: kikusui@azabu-u.ac.jp.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Kikusui
mesh_terms: D000374:Aggression / Q000187:drug effects*; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D013666:Tears / Q000737:chemistry
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C525947:exocrine-gland-secreting peptide 1, mouse