Lack of neuronal nitric oxide synthase results in attention deficit hyperactivity disorder-like behaviors in mice.
Lack of neuronal nitric oxide synthase results in attention deficit hyperactivity disorder-like behaviors in mice.
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DOI：
10.1037/bne0000031
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发表时间：
2015-02
影响因子：
1.9
通讯作者：
Heldt SA
中科院分区：
文献类型：
--
作者：
Gao Y;Heldt SA
Nitric oxide (NO) is an important molecule for the proper development and function of the central nervous system. In this study, we investigated the behavioral alterations in the neuronal nitric oxide synthase knockout mice (NOS1 KO) with a deficient NO production mechanism in the brain, characterizing it as a potential rodent model for attention deficit / hyperactivity disorder (ADHD). NOS1 KO exhibited higher locomotor activity than their wildtype counterparts in a novel environment, as measured by open field (OF) test. In a two-way active avoidance paradigm (TWAA), we found sex-dependent effects, where male KO displayed deficits in avoidance and escape behavior, sustained higher incidences of shuttle crossings and higher incidences of inter-trial interval crossings, suggesting learning and/or performance impairments. On the other hand, female KO demonstrated few deficits in TWAA. Molsidomine (MSD), a NO donor, rescued TWAA deficits in male KO when acutely administered before training. In a passive avoidance paradigm, KO of both sexes displayed significantly shorter step-through latencies after training. Further, abnormal spontaneous motor activity rhythms were found in the KO during the dark phase of the day, indicating dysregulation of rhythmic activities. These data indicate that NOS1 KO mimic certain ADHD-like behaviors and could potentially serve as a novel rodent model for ADHD.
