Elsevier

Physiology & Behavior

Volume 63, Issue 1, 31 December 1997, Pages 137-141
Physiology & Behavior

Brief Communication
D3 Dopamine Receptor-Deficient Mouse: Evidence for Reduced Anxiety

https://doi.org/10.1016/S0031-9384(97)00430-7Get rights and content

Abstract

Steiner, H., S. Fuchs and D. Accili.

D3 dopamine receptor-deficient mouse: Evidence for reduced anxiety.

PHYSIOL BEHAV 63(1) 137–141, 1998.—Mice without functional D3 dopamine receptors were examined in two animal models for anxiety: the open-field test and the elevated plus-maze test. In the open field, D3 receptor-deficient mice (D3−/−) entered the center significantly more often than normal (D3+/+) littermates, suggesting an anxiolytic-like effect of the D3 receptor mutation. Consistent with this finding, D3−/− mice entered open arms of the plus maze significantly more often and longer than D3+/+ littermates, but did not differ in closed-arm entries, an index of general activity. Heterozygous (D3+/−) animals showed intermediate behavioral changes. We interpret these results as indicative of reduced anxiety in mice without D3 receptors. Our findings thus suggest that D3 dopamine receptors are involved in the regulation of 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.

References (36)

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