Phenotypic resolution of spontaneous and D1-like agonist-induced orofacial movement topographies in congenic dopamine D1A receptor 'knockout' mice.

Abstract

A novel system was used to assess the role of D1-like dopamine receptors in distinct topographies of orofacial movements in mice with congenic D1A receptor knockout. Under spontaneous conditions, vertical jaw movements in wildtypes declined with time at a rate that was reduced in D1A mutants, while horizontal jaw movements emerged progressively in wildtypes but not in D1A mutants; tongue protrusions were absent in D1A mutants, while incisor chattering was initially reduced in D1A mutants but rose subsequently to reach the level of wildtypes. D1A receptors exert a topographically specific role in regulating individual spontaneous orofacial movements, and these involve interactions with psychomotor processes which 'sculpt' behavioural change over time. The anomalous D1-like agonist SK&F 83959, which fails to stimulate, and indeed inhibits the stimulation of adenylyl cyclase induced by dopamine, readily stimulated vertical jaw movements, tongue protrusions and incisor chattering, and these response topographies were absent in D1A mutants. These results suggest that D1A receptors may exert some form of permissive role over orofacial topographies initiated via a novel, putative D1-like site not linked to adenylyl cyclase, or that some D1A receptors might be coupled to a transduction system other than adenylyl cyclase. © 2002 Elsevier Science Ltd. All rights reserved.