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

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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

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Methylphenidate
Knockout Mice
Attention Deficit Disorder with Hyperactivity
Locomotion
Animal Models
Methamphetamine
Atomoxetine Hydrochloride
Pharmacology

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

Toriumi, Kazuya ; Tanaka, Junko ; Mamiya, Takayoshi ; Alkam, Tursun ; Kim, Hyoung Chun ; Nitta, Atsumi ; Nabeshima, Toshitaka. / Shati/Nat8l knockout mice show behavioral deficits ameliorated by atomoxetine and methylphenidate. In: Behavioural Brain Research. 2018 ; Vol. 339. pp. 207-214.
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Shati/Nat8l knockout mice show behavioral deficits ameliorated by atomoxetine and methylphenidate. / Toriumi, Kazuya; Tanaka, Junko; Mamiya, Takayoshi; Alkam, Tursun; Kim, Hyoung Chun; Nitta, Atsumi; Nabeshima, Toshitaka.

In: Behavioural Brain Research, Vol. 339, 26.02.2018, p. 207-214.

Research output: Contribution to journalArticle

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AU - Tanaka, Junko

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