Lack of neuronal nitric oxide synthase results in attention deficit hyperactivity disorder-like behaviors in mice

Yudong Gao, Scott Heldt

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 NO synthase knockout mice (NOS1 KO) with a deficient NO production mechanism in the brain, characterizing it asa 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 2-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 intertrial 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 mimics certain ADHD-like behaviors and could potentially serve as a novel rodent model for ADHD.

Original languageEnglish (US)
Pages (from-to)50-61
Number of pages12
JournalBehavioral Neuroscience
Volume129
Issue number1
DOIs
StatePublished - Jan 1 2015

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Nitric Oxide Synthase Type I
Attention Deficit Disorder with Hyperactivity
Rodentia
Nitric Oxide
Molsidomine
Avoidance Learning
Nitric Oxide Donors
Incidence
Locomotion
Knockout Mice
Motor Activity
Central Nervous System
Learning
Brain

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

Lack of neuronal nitric oxide synthase results in attention deficit hyperactivity disorder-like behaviors in mice. / Gao, Yudong; Heldt, Scott.

In: Behavioral Neuroscience, Vol. 129, No. 1, 01.01.2015, p. 50-61.

Research output: Contribution to journalArticle

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