| Co-Investigator(Kenkyū-buntansha) |
IKEDA Hiroko Nihon University, School of Dentistry, Pharmacology, Assistant, 歯学部, 助手 (70297844)
SAIGUSA Tadashi Nihon University, School of Dentistry, Pharmacology, Lecturer, 歯学部, 講師 (50277456)
KOSHIKAWA Noriaki Nihon University, School of Dentistry, Pharmacology, Professor, 歯学部, 教授 (80130491)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Using a novel procedure, the regulation of individual topographies of orofacial movement in the mouse by oppositional vs cooperative/synergistic D1-like : D2-like dopamine receptor interactions was studied. The D1-like agonists SK&F 38393, which acts via IP3 system, and SK&F 83959, which acts via both camp and IP3 systems, each induced vertical but not horizontal jaw movements, together with tongue protrusions and incisor chattering; however, SK&F 82958 induced a different profile which, consistent with other neurochemical and neurophysiological studies, suggests that this agent shows anomalous properties relative to other D1-like agonists. When given alone, the D2-like agonist quinpirole reduced horizontal jaw movements and incisor chattering. On co-administration, both SK&F 38393-and SK&F 83959-induced vertical jaw movements and tongue protrusions were inhibited by quinpirole, while SK&F 82958 again showed an anomalous profile. These findings indicate that in the mouse, vertical jaw
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movements and tongue protrusions are regulated by oppositional D1-like : D2-like interactions, and appear to involve a D1-like receptor that is not coupled to adenylyl cyclase, while horizontal jaw movements are inhibited by D2-like receptors. Additionally, results obtained using SK&F 82958 as a probe for D1-like mechanisms should be treated with considerable caution unless confirmed using other D1-like agonists. And using the same system, the role of D2-like dopamine receptors in distinct topographies of orofacial movement was assessed in mutant mice with congenic D2 vs D3 receptor knockout, and compared with findings in D1A mutants. Under spontaneous conditions, D2 mutants evidenced increased vertical jaw movements and unaltered horizontal jaw movements, with reductions in tongue protrusions and incisor chattering ; in D3 mutants, only incisor chattering was reduced. Given previous evidence that D1A mutants evidence reduced horizontal but not vertical jaw movements, this indicates that apparent oppositional D1-like : D2-like interactions in the regulation of composited jaw movements may in fact reflect the independent actions of D2 receptors to inhibit vertical jaw movements and of D1A receptors to facilitate horizontal jaw movements. Effects of the D2-like agonist RU 24213 to exert greater reduction in horizontal than in vertical jaw movements were not altered prominently in either D2 or D3 mutants. The D1-like agonists A 68930 and SK&F 83959 induced vertical jaw movements, tongue protrusions and incisor chattering ; induction of tongue protrusions by A 68930 was reduced in D2 mutants. D2 receptors exert topographically specific regulation of orofacial movements in a manner distinct from their D1A counterparts, while D3 receptors exert only minor regulation of such movements. Less
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