title: Unusual social behavior in HPC-1/syntaxin1A knockout mice is caused by disruption of the oxytocinergic neural system.
abstract: HPC-1/syntaxin1A (STX1A), a neuronal soluble N-ethylmaleimide-sensitive fusion attachment protein receptor, contributes to neural function in the CNS by regulating transmitter release. Recent studies reported that STX1A is associated with human neuropsychological disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder. Previously, we showed that STX1A null mutant mice (STX1A KO) exhibit neuropsychological abnormalities, such as fear memory deficits, attenuation of latent inhibition, and unusual social behavior. These observations suggested that STX1A may be involved in the neuropsychological basis of these abnormalities. Here, to study the neural basis of social behavior, we analyzed the profile of unusual social behavior in STX1A KO with a social novelty preference test, which is a useful method for quantification of social behavior. Interestingly, the unusual social behavior in STX1A KO was partially rescued by intracerebroventricular administration of oxytocin (OXT). In vivo microdialysis studies revealed that the extracellular OXT concentration in the CNS of STX1A KO was significantly lower compared with wild-type mice. Furthermore, dopamine-induced OXT release was reduced in STX1A KO. These results suggested that STX1A plays an important role in social behavior through regulation of the OXTergic neural system. Dopamine (DA) release is reduced in CNS of syntaxin1A null mutant mice (STX1A KO). Unusual social behavior was observed in STX1A KO. We found that oxytocin (OXT) release, which was stimulated by DA, was reduced and was rescued the unusual social behavior in STX1A KO was rescued by OXT. These results indicated that STX1A plays an important role in promoting social behavior through regulation of DA-induced OXT release in amygdala.
authors.affiliation: Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Sanada
authors.affiliation: Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.|Radioisotope Laboratory, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Kofuji
authors.affiliation: Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Akagawa
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017551:Microdialysis; D010052:Ovariectomy; D010121:Oxytocin / Q000378:metabolism* / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D012920:Social Behavior Disorders / Q000235:genetics* / Q000473:pathology*; D050827:Syntaxin 1 / Q000172:deficiency* / Q000235:genetics
chemical_list: D048588:Benzoxazines; D018765:Dopamine Uptake Inhibitors; C096766:L 371257; C576074:OXTR protein, mouse; D010879:Piperazines; D010880:Piperidines; D018045:Receptors, Oxytocin; C494214:Stx1a protein, mouse; D050827:Syntaxin 1; D010121:Oxytocin; C043425:vanoxerine; D004298:Dopamine
keywords: HPC-1/syntaxin 1A; SNARE protein; in vivo microdialysis; knockout mice; oxytocin; social behavior