Abstract
According to the dopamine (DA) hypothesis of schizophrenia and the strong evidence for decreased cerebral lateralization in schizophrenic patients, we postulated that hyperactivity of the dopaminergic system could be associated with a reduced behavioral lateralization in mice. Mice lacking the dopamine transporter (DAT) gene were used as a genetic model of persistent hyperdopaminergia. The DAT null mutation was transferred on C57BL/6JOrl (B6) and DBA/2JOrl (D2) inbred backgrounds for more than 10 generations of backcrossing to derive three DAT strains, B6, D2, and B6 × D2(F1). Adult mutant mice of the three DAT strains and their littermates were tested for paw preference using Collins' protocol. Our results demonstrated that, whatever the genetic background, persistent hyperdopaminergia directly impairs the degree of lateralization without affecting the direction. Our results support the degree of lateralization as a good candidate phenotype to further improve genetic analysis of cerebral lateralization in normal and pathological conditions.
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Acknowledgements
We are grateful to C Betancur, B Etain, M Leboyer, and F Mathieu for helpful comments on the manuscript, and C Sais for her expert technical assistance. We thank L Hillard and E Rougeron for animal care. This work was supported by INSERM and the Fondation pour la Recherche Médicale. EM was supported by a fellowship from the Ministère de l'Education Nationale, de la Recherche et de la Technologie.
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Morice, E., Denis, C., Macario, A. et al. Constitutive Hyperdopaminergia is Functionally Associated with Reduced Behavioral Lateralization. Neuropsychopharmacol 30, 575–581 (2005). https://doi.org/10.1038/sj.npp.1300570
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DOI: https://doi.org/10.1038/sj.npp.1300570
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