Constitutive and Conditional Mutant Mouse Models for Understanding Dopaminergic Regulation of Orofacial Movements: Emerging Insights and Challenges
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概要
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Among numerous mechanisms implicated in the regulation of orofacial movements, dopamine-containing neurons have received the most extensive study. Here we review the effects of a) constitutive knockout of D<SUB>1–5</SUB> dopamine receptors and b) conditional mutations with progressive ablation of D<SUB>1</SUB> receptor–expressing cells, on the topography of spontaneous and D<SUB>1</SUB>-like agonist–induced orofacial movements. In constitutive knockouts, D<SUB>1</SUB> and D<SUB>2</SUB> exert primary roles in regulating horizontal and vertical jaw movements, respectively, in opposite directions; in contrast, both D<SUB>1</SUB> and D<SUB>2</SUB> receptors regulate tongue protrusions and incisor chattering, in the same direction. D<SUB>3</SUB> and D<SUB>5</SUB> receptors play more subtle roles in regulating orofacial movements, while D<SUB>4</SUB> receptors do not play any material role. Progressive loss of forebrain D<SUB>1</SUB> receptor–expressing cells in CamKIIa/Cre D<SUB>1</SUB>Tox mutants is associated primarily with decreases in head and vibrissae movements, while progressive loss of striatal D<SUB>1</SUB> receptor–expressing cells in DARPP-32/Cre D<SUB>1</SUB>Tox mutants is associated primarily with reductions in jaw movements and tongue protrusions but increases in head and vibrissae movements. Further application of constitutive and particularly conditional mutants may clarify further not only dopaminergic regulation of orofacial movements but also the pathophysiology of orofacial dysfunction in Huntington’s disease and Parkinson’s disease.
- 公益社団法人 日本薬理学会の論文
著者
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Waddington John
Molecular & Cellular Therapeutics And Rcsi Research Institute Royal College Of Surgeons In Irela
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Koshikawa Noriaki
Department Of Pharmacology Dental Research Center Nihon University School Of Dentistry
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Tomiyama Katsunori
Advanced Research Institute for the Sciences and Humanities, Nihon University, Japan
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Drago John
Florey Neuroscience Institutes, University of Melbourne, Australia
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