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Link to original content: https://pubmed.ncbi.nlm.nih.gov/10531457
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. 1999 Nov 1;19(21):9550-6.
doi: 10.1523/JNEUROSCI.19-21-09550.1999.

Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli

S C Dulawa  1 , D K Grandy, M J Low, M P Paulus, M A Geyer
Affiliations

Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli

S C Dulawa et al. J Neurosci. .

Abstract

The involvement of dopamine neurotransmission in behavioral responses to novelty is suggested by reports that reward is related to increased dopamine activity, that dopamine modulates exploratory behavior in animals, and that Parkinson's disease patients report diminished responses to novelty. Some studies have reported that polymorphisms of the human dopamine D4 receptor (D4R) gene are associated with personality inventory measures of the trait called "novelty-seeking". To explore a potential role for the D4R in behavioral responses to novelty, we evaluated D4R-knock-out (D4R-/-) and wild-type (D4R+/+) mice in three approach-avoidance paradigms: the open field, emergence, and novel object tests. These three paradigms differ in the degree to which they elicit approach, or exploratory behavior, and avoidance, or anxiety-related behavior. Thus, we used these three tests to determine whether the D4R primarily influences the exploratory or the anxious component of responses to approach-avoidance conflicts. D4R-/- mice were significantly less behaviorally responsive to novelty than D4R+/+ mice in all three tests. The largest phenotypic differences were observed in the novel object test, which maximizes approach behavior, and the smallest phenotypic differences were found in the open field test, which maximizes avoidance behavior. Hence, D4R-/- mice exhibit reductions in behavioral responses to novelty, reflecting a decrease in novelty-related exploration.

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Figures

Fig. 1.
Fig. 1.
Regions within the open field apparatus for the open field, emergence, and novel object tests formed by computer overlaid grid lines (as viewed from above). The gray rectangle in the emergence test represents the cylinder; thegray circle in the novel object test represents the novel cup.
Fig. 2.
Fig. 2.
Motor activity. Total locomotor activity in the emergence, novel object, and open field tests is shown for D4R+/+ and D4R−/− mice. Values are means ± SEM. *p < 0.05 versus D4R+/+ group with ANOVA.
Fig. 3.
Fig. 3.
Emergence test. Exploratory measures of the emergence test are shown for D4R+/+ (n = 61) and D4R−/− mice (n = 75). The latency to emerge from the cylinder in seconds (a), the total time spent in the cylinder in seconds (b), the total number of entries into the cylinder (c), and the MTIC in seconds (d) are shown for both genotypes. Values are means ± SEM. *p < 0.05 versus D4R+/+ group with ANOVA; #p < 0.05 versus D4R+/+ group with ANCOVA.
Fig. 4.
Fig. 4.
Cylinder entries: sex differences. The number of entries into the cylinder during the emergence test is shown for male D4R+/+ (n = 31), male D4R−/− (n = 43), female D4R+/+ (n = 28), and female D4R−/− mice (n = 29). Values are means ± SEM. *p < 0.05 versus female D4R+/+ group with ANOVA; +p < 0.05 versus male D4R+/+ group with ANOVA.
Fig. 5.
Fig. 5.
Novel object test. The percentage of time spent in the center region (a) and the percentage of center entries (b) are shown for D4R+/+ (n = 59) and D4R−/− mice (n = 72) for both environmental conditions of the novel object test. Values are means ± SEM. *p < 0.05 genotype × condition interaction with ANOVA; #p < 0.05 genotype × condition with ANCOVA.
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