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: Fluid licking in mice is an example of a rhythmic behavior thought to be under the control of a central pattern generator. Inbred strains of mice have been shown to differ in mean or modal interlick interval (ILI) duration, suggesting a genetic-based variation. We investigated water licking in the commonly used inbred strains C57BL/6J (B6) and DBA/2J (D2), using a commercially available contact lickometer. Results from 20-min test sessions indicated that D2 mice lick at a faster rate than B6 mice (10.6 licks/s vs. 8.5 licks/s), based on analysis of the distribution of short-duration ILIs (50-160 ms). This strain difference was independent of sex, extent of water deprivation or total number of licks. D2 mice also displayed a faster lick rate when the strains were tested with a series of brief (5 s) trials. However, when ingestion over the entire 20-min session was analyzed, it was evident that D2 mice had an overall slower rate of ingestion than B6 mice. This was because of the tendency for D2 mice to have more very long pauses (>30 s) between sequences of licking bursts. Overall, it appeared that D2 mice licked more efficiently, ingesting more rapidly during excursions to the spout that were fewer and farther between.Genes Brain and Behavior 10/2007; 6(7):619-27. DOI:10.1111/j.1601-183X.2006.00293.x
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ABSTRACT: Given the critical role of dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein of 32 kDa (DARPP-32) in the regulation of dopaminergic function, DARPP-32-null mutant mice congenic on the inbred C57BL/6 strain for 10 generations were examined phenotypically for their ethogram of responsivity to the selective D2-like receptor agonist RU 24213 (N-n-propyl-N-phenylethyl-p-3-hydroxyphenylethylamine) and the selective D2-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide), using procedures that resolve all topographies of behavior in the natural repertoire. After vehicle challenge, levels of sniffing and rearing seated were reduced in DARPP-32 mutants; the injection procedure seems to constitute a "stressor" that reveals phenotypic effects of DARPP-32 deletion not apparent under natural conditions. Topographical effects of 0.3 to 10.0 mg/kg RU 24213, primarily induction of sniffing and ponderous locomotion with accompanying reductions in rearing, grooming, sifting and chewing, were not altered to any material extent in DARPP-32-null mice. However, topographical effects of 0.005 to 0.625 mg/kg YM 09151-2, namely, reduction in sniffing, locomotion, rearing, grooming, and chewing but not sifting, were essentially absent in DARPP-32 mutants. Thus, the D2-like receptor agonist-mediated ethogram was essentially conserved, whereas major elements of the corresponding D2-like receptor antagonist-mediated ethogram were essentially absent in DARPP-32-null mice. This suggests some relationship between 1) extent of tonic dopaminergic activation of DARPP-32 mechanisms and 2) compensatory mechanisms consequent to the developmental absence of DARPP-32, which may emerge to act differentially on individual elements of the DARPP-32 system. Critically, the present data indicate that phenotypic effects of a given gene deletion using an agonist acting on the system disrupted cannot be generalized to a corresponding antagonist, and vice versa.Journal of Pharmacology and Experimental Therapeutics 10/2004; 310(3):1281-7. DOI:10.1124/jpet.104.068957
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ABSTRACT: Using a novel procedure, the regulation of individual topographies of orofacial movement in the mouse by oppositional versus cooperative/synergistic D1-like: D2-like dopamine receptor interactions was studied. The D1-like agonists SK&F 38393 and SK&F 83959 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 coadministration, 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 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, whereas 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 until they are confirmed using other D1-like agonists.Journal of Psychopharmacology 01/2005; 18(4):484-95. DOI:10.1177/0269881104047275