Abstract
D1A-null mice were backcrossed over 14 generations into a C57BL/6 background to result in essential elimination (to <0.005%) of any contribution from the 129/Sv component of their initially mixed (129/Sv×C57BL/6) background. Their phenotype was assessed using an ethologically based approach that resolves each individual topography of behaviour in the natural repertoire. Habituation of sniffing, locomotion, rearing seated, and rearing to wall in wild types over several hours was profoundly retarded in congenic D1A 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.
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Acknowledgements
These studies were supported by the Research Committee of the Royal College of Surgeons in Ireland, the Stanley Medical Research Institute and a Galen Fellowship from the Irish Brain Research Foundation, in the Institute of Biopharmaceutical Sciences under the Higher Education Authority's Programme for Research in Third Level Institutions. We thank Hoechst-Marion-Roussel for RU 24213 and Yamanouchi for YM 09151-2. SK&F 83959 was provided by Research Biochemicals International as part of the Chemical Synthesis Program of the National Institute of Mental Health, Contract No. N01MH30003.
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McNamara, F., Clifford, J., Tighe, O. et al. Congenic D1A Dopamine Receptor Mutants: Ethologically Based Resolution of Behavioural Topography Indicates Genetic Background as a Determinant of Knockout Phenotype. Neuropsychopharmacol 28, 86–99 (2003). https://doi.org/10.1038/sj.npp.1300008
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DOI: https://doi.org/10.1038/sj.npp.1300008
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