Comparative phenotypic resolution of spontaneous, D2-like and D1-like agonist-induced orofacial movement topographies in congenic mutants with dopamine D2 vs. D3 receptor "knockout".
ABSTRACT Using a novel 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 show 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.
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ABSTRACT: Elucidating the relative involvement of individual dopamine receptor subtypes in the regulation of behavior has been made difficult by anomalies at the psychopharmacology–molecular biology interface; specifically, the extent to which gene cloning has revealed greater diversity in dopamine receptor typology beyond the original D1/D2 classification, to include individual members of D1-like (D1 and D5) and D2-like (D2Short, D2Long, D3, and D4) families, has not been matched by similar progress in developing selective agonists and antagonists for these receptors. Thus, although classical psychopharmacological approaches have been instrumental in defining dopamine-dependent behaviors at the family level, more incisive molecular genetic techniques have been required to determine the functional roles of the individual members of these families. This chapter seeks to (a) summarize the classical psychopharmacology of dopamine receptor subtype function, (b) provide an overview of recent findings in dopamine receptor subtype knockouts across several domains of behavior, and (c) interpret new insights in the context of the limitations of these techniques and prior knowledge of the regulation of behavior by dopamine receptors. KeywordsDopamine receptor subtypes-Behavior-Psychopharmacology-Selective agonists and antagonists-Molecular biology-Knockouts-Knockins-Transgenics-Mutant models11/2009: pages 323-371;
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ABSTRACT: The role of D(1)-like [D(1), D(5)] and D(2)-like [D(2), D(3), D(4)] dopamine receptors and dopamine transduction via DARPP-32 in topographies of orofacial movement was assessed in restrained mice with congenic D(4) vs. D(5) receptor vs. DARPP-32 'knockout'. D(4) and DARPP-32 mutants evidenced no material phenotype; also, there were no alterations in topographical responsivity to either the selective D(2)-like agonist RU 24213 or the selective D(1)-like agonist SK and F 83959. In contrast, D(5) mutants evidenced an increase in spontaneous vertical jaw movements, which habituated more slowly than in wildtypes, and a decrease in horizontal jaw movements; topographical responsivity to SK and F 83959 and RU 24213 was unaltered. D(5) receptors regulate distinct topographies of vertical and horizontal jaw movement in an opposite manner. In assuming that the well-recognised role of the D(1)-like family in regulating orofacial movements involves primarily D(1) receptors, a role for their D(5) counterparts may have been overlooked.European Neuropsychopharmacology 09/2006; 16(6):437-45. · 4.60 Impact Factor
- Advances in Inorganic Chemistry - ADVAN INORG CHEM. 01/2009; 61:471-521.