title: Brain serotonin signaling does not determine sexual preference in male mice.
abstract: It was reported recently that male mice lacking brain serotonin (5-HT) lose their preference for females (Liu et al., 2011, Nature, 472, 95-100), suggesting a role for 5-HT signaling in sexual preference. Regulation of sex preference by 5-HT lies outside of the well established roles in this behavior established for the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). Presently, mice with a null mutation in the gene for tryptophan hydroxylase 2 (TPH2), which are depleted of brain 5-HT, were tested for sexual preference. When presented with inanimate (urine scents from male or estrous female) or animate (male or female mouse in estrus) sexual stimuli, TPH2-/- males show a clear preference for female over male stimuli. When a TPH2-/- male is offered the simultaneous choice between an estrous female and a male mouse, no sexual preference is expressed. However, when confounding behaviors that are seen among 3 mice in the same cage are controlled, TPH2-/- mice, like their TPH2+/+ counterparts, express a clear preference for female mice. Female TPH2-/- mice are preferred by males over TPH2+/+ females but this does not lead to increased pregnancy success. In fact, if one or both partners in a mating pair are TPH2-/- in genotype, pregnancy success rates are significantly decreased. Finally, expression of the VNO-specific cation channel TRPC2 and of CNGA2 in the MOE of TPH2-/- mice is normal, consistent with behavioral findings that sexual preference of TPH2-/- males for females is intact. In conclusion, 5-HT signaling in brain does not determine sexual preference in male mice. The use of pharmacological agents that are non-selective for the 5-HT neuronal system and that have serious adverse effects may have contributed historically to the stance that 5-HT regulates sexual behavior, including sex partner preference.
authors.affiliation: Research & Development Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America; Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, United States of America.
authors.forename: Mariana
authors.initials: M
authors.lastname: Angoa-Pérez
authors.affiliation: Research & Development Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America; Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, United States of America.
authors.forename: Nieves
authors.initials: N
authors.lastname: Herrera-Mundo
authors.affiliation: Research & Development Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America; Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kane
authors.affiliation: Research & Development Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America; Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, United States of America.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Sykes
authors.affiliation: Research & Development Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America; Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, United States of America.
authors.forename: John H
authors.initials: JH
authors.lastname: Anneken
authors.affiliation: Research & Development Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America; Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, United States of America.
authors.forename: Dina M
authors.initials: DM
authors.lastname: Francescutti
authors.affiliation: Research & Development Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America; Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, United States of America.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Kuhn
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012701:Serotonin / Q000378:metabolism*; D012726:Sexual Behavior, Animal; D015398:Signal Transduction; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000502:physiology
chemical_list: D012701:Serotonin; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase