Congenic D1A Dopamine Receptor Mutants: Ethologically Based Resolution of Behavioural Topography Indicates Genetic Background as a Determinant of Knockout Phenotype

摘要

D1A-null mice were backcrossed over 14 generations into a C57BL/6 background to result in essential elimination (to 1A mutants; conversely, rearing free and sifting were essentially abolished. Resultant increases in individual topographies of behaviour were substantially greater in congenic D1A mutants than in those on a mixed background. This phenotype was little altered by the selective D1-like antagonist SCH 23390 and could not be blocked by the selective D2-like antagonist YM 09151-2. The selective D1-like agonist SK&F 83959 could not further elevate those behaviours already heightened in congenic D1A mutants, while the induction of stereotyped sniffing and plodding locomotion by the selective D2-like agonist RU 24213 was disrupted. Genetic background appears to modulate critically the magnitude but not the general nature of the D1A-null phenotype, which may involve compensatory processes independent of other D1-like or D2-like receptors.