TY - JOUR
T1 - Shati/Nat8l knockout mice show behavioral deficits ameliorated by atomoxetine and methylphenidate
AU - Toriumi, Kazuya
AU - Tanaka, Junko
AU - Mamiya, Takayoshi
AU - Alkam, Tursun
AU - Kim, Hyoung Chun
AU - Nitta, Atsumi
AU - Nabeshima, Toshitaka
N1 - Funding Information:
This study was supported by the following: Grants-in-aid for Young Scientists (B) (26870878), Scientific Research (26460240 and 15K08218, 16K10195, 17H04252), Joint Research Project under the Japan-Korea Basic Scientific Cooperation Program, Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented researchers (S2603) from the Japan Society for the Promotion of Science (JSPS), Research Grants from the Ministry of Health, Labor, and Welfare of Japan, research grant from the SRF.
Funding Information:
This study was supported by the following: Grants-in-aid for Young Scientists (B) ( 26870878 ), Scientific Research ( 26460240 and 15K08218 , 16K10195 , 17H04252 ), Joint Research Project under the Japan-Korea Basic Scientific Cooperation Program, Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented researchers (S2603) from the Japan Society for the Promotion of Science (JSPS) , Research Grants from the Ministry of Health, Labor, and Welfare of Japan , research grant from the SRF.
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/2/26
Y1 - 2018/2/26
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbr.2017.11.040
DO - 10.1016/j.bbr.2017.11.040
M3 - Article
C2 - 29203337
AN - SCOPUS:85037032917
VL - 339
SP - 207
EP - 214
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
ER -