Dopamine autoreceptor regulation of release and uptake in mouse brain slices in the absence of D3 receptors
Section snippets
Animals
The mice used in this study were of the mixed strain C57B6/129SvJ (F2 generation) and were 4–8-month-old males. Both the DAT-KO (DAT−/−) (Giros et al., 1996) and D3-KO mice were generated by homologous recombination. Food and water was provided ad libitum. Animal care was in accordance with institutional guidelines.
Locomotion measurements
Locomotor activity measurements were measured with an Omnitech monitor, a device equipped with infrared photobeam detectors. Horizontal activity was measured as total distance
Generation of D3-KO mice
A genomic clone containing exon 1 of the murine D3 receptor gene was isolated from a 129/SvJ genomic library (Stratagene) with a PCR-generated probe derived from exon 1 sequences of the rat D3 receptor gene (Giros et al., 1991). In the targeting construct D (Fig. 1A), exon 1 is replaced by the neomycin gene cassette under the control of the PGK promoter (PGK-neo) (Adra et al., 1987). A MC1-TK gene was positioned upstream for negative selection with gancyclovir. The total length of homology is
Discussion
These investigations confirm previous reports (Accili et al., 1996, Xu et al., 1997) that mice with a genetic deletion of the D3 receptor are hyper-responsive to a novel environment. While measurable, the hyperactivity is modest, and in fact has gone unnoticed by some investigators (Jung et al., 1999). Consistent with the role of DA in behavioral activation (Carlsson, 1993), the hyperactivity in D3-KO mice is accompanied by elevated concentrations of striatal extracellular DA, in agreement with
Acknowledgements
We gratefully acknowledge Dr. Peter Fuchs and Dr. Adolf Himmler (Bender Wien, Vienna, Austria) for contributing the inactivation construct used to generate D3-KO mice. This research was supported by NIH (NS 15841 to R.M.W. and NS 19576 to M.G.C.). M.G.C. is an investigator of the Howard Hughes Medical Institute.
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