| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Attention-deficit hyperactive disorder (ADHD) is a developmental disorder that was characterized by locomotor hyperactivity, impulsiveness, and inattention. Our recent study demonstrated that male rat offspring prenatally exposed to 5-bromo-2'-deoxyuridine (BrdU) showed locomotor hyperactivity. We further characterized the behavioral abnormality of BrdU rats using a home cage, an open field, Y-maze, and elevated plus maze and evaluated its suitability as an animal model of ADHD. Rats were treated with BrdU 50 mg/kg, IP or carboxymethylcellulose (CMC), its vehicle, on gestational days 9 through 15, and their offspring (BrdU rats and CMC rats, respectively) were subjected to behavioral tests at 5 to 6 weeks of age. A home cage locomotor activity increased when lights were out and gradually decreased during a night cycle in CMC rats. In BrdU rats, locomotor activity was kept increased throughout a night cycle, suggesting continuous locomotor hyperactivity. In the elevated plus maze task,
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the number of open arm entries and time spent per one open arm entry, both of which are indices of impulsivity, were significantly increased in BrdU rats when compared with those of CMC rats. In the Y-maze test, spontaneous alternation behavior was significantly lowered in BrdU rats. There were no differences in the long-term potentiation, a cellular mechanism of memory, between BrdU and CMC rats. Thus, lowered spontaneous alternation behavior in BrdU rats was not caused by a deficiency of short-term memory but by attention deficit. Methylphenidate, which is commonly used drug for ADHD, increased rather than decreased locomotor activity in BrdU rats as well as CMC rats, with the BrdU rats showing greater sensitivity. Paroxetine and desipramine normalized behavioral abnormality in an open field and/or elevated plus maze. These results suggest that BrdU rat is a novel model of ADHD with resistance to methylphenidate treatment. Serotonergic and noradrenergic neuronal dysfunction may be, at least in part, the cause of the behavioral abnormalities. Less
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