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

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• 作者：Abby Adamczyk^a ; Rebeca Mejias^a ; Kogo Takamiya^b ; ¹ ; Jennifer Yocum^c ; Irina N. Krasnova^d ; Juan Calderon^a ; Jean Lud Cadet^d ; Richard L. Huganir^b ; Mikhail V. Pletnikov^c ; Tao Wang^a ; ^{twang9@jhmi.edu}
• 关键词：AMPA ; 2-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid ; GluA3 ; AMPA glutamate receptor 3 ; NE ; norepinephrine ; DA ; dopamine ; DOPAC ; 3 ; 4-dihydroxyphenylacetic acid ; HVA ; homovanillic acid ; 5-HT ; serotonin ; 5-HIAA ; 5-hydroxyindoleacetic acid
• 刊名：Behavioural Brain Research
• 出版年：2012
• 出版时间：1 April, 2012
• 年：2012
• 卷：229
• 期：1
• 页码：265-272
• 全文大小：585 K

文摘

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.