title: Anxiogenic drug administration and elevated plus-maze exposure in rats activate populations of relaxin-3 neurons in the nucleus incertus and serotonergic neurons in the dorsal raphe nucleus.
abstract: Anxiety is a complex and adaptive emotional state controlled by a distributed and interconnected network of brain regions, and disruption of these networks is thought to give rise to the behavioral symptoms associated with anxiety disorders in humans. The dorsal raphe nucleus (DR), which contains the majority of forebrain-projecting serotonergic neurons, is implicated in the control of anxiety states and anxiety-related behavior via neuromodulatory effects on these networks. Relaxin-3 is the native neuropeptide ligand for the Gi/o-protein-coupled receptor, RXFP3, and is primarily expressed in the nucleus incertus (NI), a tegmental region immediately caudal to the DR. RXFP3 activation has been shown to modulate anxiety-related behavior in rodents, and RXFP3 mRNA is expressed in the DR. In this study, we examined the response of relaxin-3-containing neurons in the NI and serotonergic neurons in the DR following pharmacologically induced anxiety and exposure to an aversive environment. We administered the anxiogenic drug FG-7142 or vehicle to adult male Wistar rats and, 30 min later, exposed them to either the elevated plus-maze or home cage control conditions. Immunohistochemical detection of c-Fos was used to determine activation of serotonergic neurons in the DR and relaxin-3 neurons in the NI, measured 2h following drug injection. Analysis revealed that FG-7142 administration and exposure to the elevated plus-maze are both associated with an increase in c-Fos expression in relaxin-3-containing neurons in the NI and in serotonergic neurons in dorsal and ventrolateral regions of the DR. These data are consistent with the hypothesis that relaxin-3 systems in the NI and serotonin systems in the DR interact to form part of a network involved in the control of anxiety-related behavior.
authors.affiliation: School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, Australia. Electronic address: a.lawther@latrobe.edu.au.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lawther
authors.affiliation: School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: M L
authors.initials: ML
authors.lastname: Clissold
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ma
authors.affiliation: School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Kent
authors.affiliation: Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Lowry
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: A L
authors.initials: AL
authors.lastname: Gundlach
authors.affiliation: School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, Australia. Electronic address: m.hale@latrobe.edu.au.
authors.forename: M W
authors.initials: MW
authors.lastname: Hale
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D002452:Cell Count; D065847:Dorsal Raphe Nucleus / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011903:Raphe Nuclei / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D012065:Relaxin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014365:Tryptophan Hydroxylase
chemical_list: D014151:Anti-Anxiety Agents; D002243:Carbolines; D016760:Proto-Oncogene Proteins c-fos; D012701:Serotonin; C035874:FG 7142; D012065:Relaxin; D014365:Tryptophan Hydroxylase
keywords: anxiety; dorsal raphe nucleus; elevated plus-maze; nucleus incertus; relaxin-3; serotonin