GluA3-deficiency in mice is associated with increased social and aggressive behavior and elevated dopamine in striatum

Abby Adamczyk, Rebeca M Mejias-Estevez, Kogo Takamiya, Jennifer Yocum, Irina N. Krasnova, Juan Calderon, Jean Lud Cadet, Richard L. Huganir, Mikhail Pletnikov, Tao Wang

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalBehavioural Brain Research
Issue number1
StatePublished - Apr 1 2012


  • Aggression
  • Dopamine
  • GluA3
  • Glutamate receptor
  • Mice
  • Olfactory bulb
  • Serotonin
  • Sociability
  • Social interaction
  • Striatum

ASJC Scopus subject areas

  • Behavioral Neuroscience


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