Shati/Nat8l knockout mice show behavioral deficits ameliorated by atomoxetine and methylphenidate

Kazuya Toriumi, Junko Tanaka, Takayoshi Mamiya, Tursun Alkam, Hyoung Chun Kim, Atsumi Nitta, Toshitaka Nabeshima

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We previously identified a novel molecule, SHATI/NAT8L, as having an inhibitory effect on methamphetamine dependence. We generated Shati/Nat8l knockout (KO) mice and found that they showed neurochemical changes and behavioral abnormalities related to attention deficit/hyperactivity disorder (AD/HD). In this study, we assessed validities of the Shati/Nat8l KO mice as a new animal model for AD/HD through a behavioral pharmacology approach. We conducted a locomotor activity test in a novel environment, a cliff avoidance test, and an object-based attention assay using Shati/Nat8l KO mice at the ages of 4 and 8 weeks. We found that at the ages of both 4 and 8 weeks, Shati/Nat8l KO mice showed hyperactivity in locomotor activity test, shortened jumping latency in cliff avoidance test, and lower recognition index in object-based recognition test. Moreover, we evaluated the effects of atomoxetine (ATX) and methylphenidate (MPH) on the behavioral deficits in Shati/Nat8l KO mice. As the result, almost all behavioral deficits were improved by the treatment of both ATX and MPH. Our findings suggest that Shati/Nat8l KO mice have an impaired neural system similar to AD/HD pathophysiology. Shati/Nat8l KO mice might serve as a novel and a useful animal model for the pathophysiology of AD/HD.

Original languageEnglish
Pages (from-to)207-214
Number of pages8
JournalBehavioural Brain Research
Volume339
DOIs
Publication statusPublished - 26-02-2018

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

Toriumi, K., Tanaka, J., Mamiya, T., Alkam, T., Kim, H. C., Nitta, A., & Nabeshima, T. (2018). Shati/Nat8l knockout mice show behavioral deficits ameliorated by atomoxetine and methylphenidate. Behavioural Brain Research, 339, 207-214. https://doi.org/10.1016/j.bbr.2017.11.040