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Behavioral Pharmacology

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Impairment of social behavior in HPC-1/syntaxin1A knockout mice relate with reduction of DA and OXT release

  • P3-354
  • 藤原 智徳 / Tomonori Fujiwara:1 小藤 剛史 / Takefumi Kofuji:2 真田 ますみ / Masumi Sanada:1 赤川 公朗 / Kimio Akagawa:1 
  • 1:杏林大学・医・細胞生理 / Dept Cell Physiol., Kyorin Univ. Sch. of Med., Tokyo, Japan 2:杏林大学・医・RI部門 / Radio Isotope Lab., Kyorin Univ. Sch. of Med., Tokyo, Japan 

HPC-1/syntaxin1A (STX1A) is believed to regulate synaptic transmission as a neuronal t-SNARE. Previously, we generated STX1A gene knockout mice. Surprisingly, homozygous mutant mice (STX1A KO) normally developed and basal synaptic transmission in cultured neurons appeared to be normal, but monoamines release were reduced. Interestingly, STX1A KO showed neuropsychological abnormalities, suggesting relation between STX1A and human psychological disorders.
Here, we focused on social behavioral profiles in STX1A KO. In social interaction test, STX1A KO showed a characteristic no decline of the time interacting with intruder mouse unlike in WT. In social novelty preference test, there was no difference between the time investigating to novel and familiar mouse in STX1A KO unlike in WT. Interestingly, these behavioral alternations in STX1A KO were partially recovered by administration of DA transporter inhibitor, D1 receptor agonist or oxytocin (OXT). Then, we analyzed DA and OXT release in STX1A KO. In vivo microdialysis studies revealed that both of extracellular DA and OXT concentrations were reduced in STX1A KO brain, suggesting reduction of DA and OXT release. We further analyzed if DA stimulation affect OXT secretion or vice versa.

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