title: Effects of lurasidone on ketamine-induced joint visual attention dysfunction as a possible disease model of autism spectrum disorders in common marmosets.
abstract: Infants with autism have difficulties performing joint visual attention (JVA), defined as following another person's pointing gesture and gaze. Some non-human primates (NHPs) can also perform JVA. Most preclinical research on autism spectrum disorders (ASD) has used rodents as animal models of this social interaction disorder. However, models using rodents fail to capture the complexity of social interactions that are disrupted in ASD. Therefore, JVA impairment in NHPs might be a more useful model of ASD. The aim of this study was to develop an appropriate and convenient ASD model with common marmosets. We first tested whether marmosets were capable of performing JVA. Subsequently, we administered ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, to induce JVA impairment and investigated the effects of lurasidone, a newer antipsychotic agent, on the JVA impairments. An apparatus was constructed using 4 white boxes, which were attached to the corners of a frame. All boxes had a hinged door, and marmosets could easily obtain a reward by pushing the door. An experimenter pointed and gazed at the boxes to inform the marmosets which box contained the reward. Their behavior was scored according to the number of incorrect choices. The JVA score was significantly higher in the cued vs. uncued tasks. Ketamine significantly decreased the JVA score, but lurasidone significantly reversed this effect. These findings suggest that this experimental system could be a useful animal model of neuropsychiatric disorders characterized by NMDA-receptor signaling, including ASD, and that lurasidone might be effective for some aspects of ASD.
authors.affiliation: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Nakako
authors.affiliation: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murai
authors.affiliation: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ikejiri
authors.affiliation: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Manato
authors.initials: M
authors.lastname: Kotani
authors.affiliation: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Manabe
authors.affiliation: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogi
authors.affiliation: Department of Behavioral and Brain Sciences, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506, Japan.
authors.forename: Naho
authors.initials: N
authors.lastname: Konoike
authors.affiliation: Department of Behavioral and Brain Sciences, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506, Japan.
authors.forename: Katsuki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. Electronic address: kazuhito-ikeda@ds-pharma.co.jp.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced* / Q000188:drug therapy*; D002144:Callithrix; D002659:Child Development Disorders, Pervasive / Q000139:chemically induced / Q000150:complications; D003463:Cues; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005260:Female; D054833:Isoindoles / Q000627:therapeutic use*; D007649:Ketamine / Q000633:toxicity*; D000069056:Lurasidone Hydrochloride; D008297:Male; D012720:Severity of Illness Index; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D054833:Isoindoles; D013844:Thiazoles; D007649:Ketamine; D000069056:Lurasidone Hydrochloride
keywords: Autism spectrum disorder; Joint visual attention; Ketamine; Lurasidone; Marmoset