RATIONALE: The thyroid hormones (T3 and T4) play a critical role in brain development, and thyroid abnormalities have been linked to a variety of psychiatric and neuropsychological disorders. Among patients with the rare genetic syndrome resistance to thyroid hormone (RTH), 40-70% meet the diagnostic criteria for attention deficit-hyperactivity disorder (ADHD). RTH is caused by a mutation in the thyroid receptor beta (Thrb) gene that results in reduced binding of T3 to its receptor and elevated concentrations of T3, T4, and thyroid-stimulating hormone. OBJECTIVES: We tested a knock-in (KI) mouse expressing a mutant TRbeta allele (TRbetaPV) for the behavioral features of ADHD and their response to methylphenidate (MPH). METHODS: The locomotor activity of the TRbetaPV KI mice was measured in activity monitors over multiple sessions. Sustained attention and the effects of MPH on attention were assessed using a vigilance task. RESULTS: The TRbetaPV KI mice are hyperactive and have learning deficits on a vigilance task. Doses of MPH that impair the vigilance performance of wild-type mice do not affect the performance of the TRbetaPV KI mice. CONCLUSIONS: The TRbetaPV KI mice provide a tool for studying the underlying neural deficits that contribute to thyroid-related neurological disorders, hyperactivity, and altered responsiveness to MPH.
RATIONALE: The thyroid hormones (T3 and T4) play a critical role in brain development, and thyroid abnormalities have been linked to a variety of psychiatric and neuropsychological disorders. Among patients with the rare genetic syndrome resistance to thyroid hormone (RTH), 40-70% meet the diagnostic criteria for attention deficit-hyperactivity disorder (ADHD). RTH is caused by a mutation in the thyroid receptor beta (Thrb) gene that results in reduced binding of T3 to its receptor and elevated concentrations of T3, T4, and thyroid-stimulating hormone. OBJECTIVES: We tested a knock-in (KI) mouse expressing a mutant TRbeta allele (TRbetaPV) for the behavioral features of ADHD and their response to methylphenidate (MPH). METHODS: The locomotor activity of the TRbetaPV KI mice was measured in activity monitors over multiple sessions. Sustained attention and the effects of MPH on attention were assessed using a vigilance task. RESULTS: The TRbetaPV KI mice are hyperactive and have learning deficits on a vigilance task. Doses of MPH that impair the vigilance performance of wild-type mice do not affect the performance of the TRbetaPV KI mice. CONCLUSIONS: The TRbetaPV KI mice provide a tool for studying the underlying neural deficits that contribute to thyroid-related neurological disorders, hyperactivity, and altered responsiveness to MPH.
Authors: E Richardson; S S Kupietz; B G Winsberg; S Maitinsky; N Mendell Journal: J Am Acad Child Adolesc Psychiatry Date: 1988-01 Impact factor: 8.829
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