title: GluA3-deficiency in mice is associated with increased social and aggressive behavior and elevated dopamine in striatum.
abstract: Glutamate signaling has been implicated in the regulation of social behavior. AMPA-glutamate receptors are assembled from four subunits (GluA1-4) of mainly GluA1/2 and GluA2/3 tetramers that form ion channels of distinct functional properties. Mice lacking GluA1 showed a reduced anxiety and male aggression. To understand the role of GluA3 in modulating social behavior, we investigated GluA3-deficient mice (Gria3-/Y) on C57BL/6J background. Compared to wild type (WT) littermates (n=14), Gria3-/Y mice (n=13) showed an increase in isolation-induced male aggression (p=0.011) in home cage resident-intruder test; an increase in sociability (p=0.01), and increase in male-male social interactions in neutral arena (p=0.005); an increase in peripheral activities in open field test (p=0.037) with normal anxiety levels in elevated plus maze and light-dark box; and minor deficits in motor and balance function in accelerating rotarod test (p=0.016) with normal grip strength. Gria3-/Y mice showed no significant deficit in spatial memory function in Morris-water maze and Y-maze tests, and normal levels of testosterone. Increased dopamine concentrations in stratum (p=0.034) and reduced serotonin turnover in olfactory bulb (p=0.002) were documented in Gria3-/Y mice. These results support a role of GluA3 in the modulation of social behavior through brain dopamine and/or serotonin signaling and different AMPA receptor subunits affect social behavior through distinct mechanisms.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, 733 North Broadway BRB 513, Baltimore, MD 21205, USA.
authors.forename: Abby
authors.initials: A
authors.lastname: Adamczyk
authors.forename: Rebeca
authors.initials: R
authors.lastname: Mejias
authors.forename: Kogo
authors.initials: K
authors.lastname: Takamiya
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yocum
authors.forename: Irina N
authors.initials: IN
authors.lastname: Krasnova
authors.forename: Juan
authors.initials: J
authors.lastname: Calderon
authors.forename: Jean Lud
authors.initials: JL
authors.lastname: Cadet
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pletnikov
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000374:Aggression / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism*; D003623:Dark Adaptation / Q000235:genetics; D004298:Dopamine / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D018737:Hand Strength / Q000502:physiology; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011930:Reaction Time / Q000235:genetics; D018091:Receptors, AMPA / Q000172:deficiency*; D012903:Smell / Q000235:genetics; D012919:Social Behavior; D013028:Space Perception / Q000502:physiology; D013739:Testosterone / Q000097:blood
chemical_list: D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; D015102:3,4-Dihydroxyphenylacetic Acid; D013739:Testosterone; D004298:Dopamine; D006719:Homovanillic Acid