Hyperactivity, impaired learning on a vigilance task, and a differential response to methylphenidate in the TRβPV knock-in mouse

William B. Siesser, Sheue Yann Cheng, Michael Mcdonald

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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 β (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 TRβ allele (TRβPV) for the behavioral features of ADHD and their response to methylphenidate (MPH). Methods: The locomotor activity of the TRβPV 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 TRβPV 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 TRβPV KI mice. Conclusions: The TRβPV KI mice provide a tool for studying the underlying neural deficits that contribute to thyroid-related neurological disorders, hyperactivity, and altered responsiveness to MPH.

Original languageEnglish (US)
Pages (from-to)653-663
Number of pages11
JournalPsychopharmacology
Volume181
Issue number4
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

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Methylphenidate
Learning
Thyroid Hormone Resistance Syndrome
Thyroid Gland
Attention Deficit Disorder with Hyperactivity
Thyroxine
Triiodothyronine
Thyrotropin
Locomotion
Nervous System Diseases
Psychiatry
Alleles
Mutation
Brain
Genes

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Hyperactivity, impaired learning on a vigilance task, and a differential response to methylphenidate in the TRβPV knock-in mouse. / Siesser, William B.; Cheng, Sheue Yann; Mcdonald, Michael.

In: Psychopharmacology, Vol. 181, No. 4, 01.10.2005, p. 653-663.

Research output: Contribution to journalArticle

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