title: RGS2 mediates the anxiolytic effect of oxytocin.
abstract: The neuropeptide oxytocin (OT) has been shown to exert multiple functions in both males and females, and to play a key role in the regulation of emotionality in the central nervous system (CNS). OT has an anxiolytic effect in the CNS of rodents and humans. However, the molecular mechanisms of this effect are unclear. Here we show that OT induced the expression of regulator of G-protein signaling 2 (RGS2), a regulatory factor for anxiety, in the central amygdala (CeA) of female mice. Bath application of OT increased RGS2 levels in slices of the amygdala of virgin mice. RGS2 levels in the CeA were higher in lactating mice than in virgin mice. In contrast, RGS2 levels in mice that had given birth did not increase when the pups were removed. Acute restraint stress for 4h induced RGS2 expression within the CeA, and local administration of an OT receptor antagonist inhibited this expression. Behavioral experiments revealed that transient restraint stress had an anxiolytic effect in wild-type females, and RGS2 levels in the CeA correlated with the anxiolytic behavior. By contrast, in the OT receptor-deficient mice, restraint stress neither increased RGS2 levels in the CeA nor had an anxiolytic effect. These results suggest that OT displays an anxiolytic effect through the induction of RGS2 expression in the CNS.
authors.affiliation: Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Okimoto
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Bosch
authors.forename: David A
authors.initials: DA
authors.lastname: Slattery
authors.forename: Konstanze
authors.initials: K
authors.lastname: Pflaum
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsushita
authors.forename: Fan-Yan
authors.initials: FY
authors.lastname: Wei
authors.forename: Masayasu
authors.initials: M
authors.lastname: Ohmori
authors.forename: Tei-ichi
authors.initials: T
authors.lastname: Nishiki
authors.forename: Iori
authors.initials: I
authors.lastname: Ohmori
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiramatsu
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsui
authors.forename: Inga D
authors.initials: ID
authors.lastname: Neumann
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D007774:Lactation / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology*; D020710:RGS Proteins / Q000378:metabolism*; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D020710:RGS Proteins; D018045:Receptors, Oxytocin; C105345:Rgs2 protein, mouse; D010121:Oxytocin