Brief CommunicationD3 Dopamine Receptor-Deficient Mouse: Evidence for Reduced Anxiety
Section snippets
Animals
D3 receptor-deficient mice were generated by targeted mutagenesis in mouse embryonic stem cells (129/SvJae; kindly provided by R. Jaenisch), as described previously [1]. Male chimeras were mated with C57BL/6J females to produce heterozygous mutants. Heterozygote matings were used to generate D3−/−, D3+/−, and D3+/+ littermates. The genotype was determined by reverse transcription-PCR [1]. Only male littermates were used in these studies. The animals examined in the open-field test were 8–12
Open-field Test
During the 15-min test, D3−/− mice entered the central square more than twice as often as D3+/+ littermates (Fig. 1AFig. 1B). The statistical analysis confirmed a significant genotype effect (p < 0.05, Kruskal–Wallis test) that was mainly due to the difference between D3−/− and D3+/+ mice (p = 0.01, Mann–Whitney U-test). This difference could be seen throughout the test but was more pronounced during the second half (Fig. 1A). As reported before [1], D3−/− mice displayed ca. 60% more crossings
Discussion
Initially, we observed that D3 receptor-deficient mice showed more locomotor activity and higher rearing rates than wildtype littermates when tested in a novel open field [1]. Open-field behavior is influenced by multiple factors, including “emotionality” or anxiety 13, 34, 36, some of which likely have genetic components 8, 18. Thus, in our expanded behavioral analysis of D3 mutants, we have included behavioral measures that take such factors into account. Our results showed that D3−/− mice
Conclusions
Our previous behavioral analysis of D3 dopamine receptor-deficient mice revealed increased locomotor activity in an open-field test, which may indicate reduced anxiety in these mice. In the present study, we further investigated the behavioral effects of the D3 receptor mutation by including additional behavioral responses that are known to be affected by anxiety: center entries in the open field and open-arm entries in the elevated plus maze. Our present results also indicate an
Acknowledgements
We thank Martha H. Cool for excellent technical assistance. This work was done in the laboratory of Charles R. Gerfen, Laboratory of Neurophysiology, National Institute of Mental Health, Bethesda, MD.
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