D₄ receptor deficiency in mice has limited effects on impulsivity and novelty seeking

Alleles of the human dopamine D₄ receptor (D₄R) gene (DRD4.7) have repeatedly been found to correlate with novelty seeking, substance abuse, pathological gambling, and attention-deficit hyperactivity disorder (ADHD). If these various psychopathologies are a result of attenuated D₄R-mediated signaling, mice lacking D₄Rs (D₄KO) should be more impulsive than wild-type (WT) mice and exhibit more novelty seeking. However, in our study, D₄KO and WT mice showed similar levels of impulsivity as measured by delay discounting performance and response inhibition on a Go/No-go test, suggesting that D₄R-mediated signaling may not affect impulsivity. D₄KO mice were more active than WT mice in the first 5 min of a novel open field test, suggesting greater novelty seeking. For both genotypes, more impulsive mice habituated less in the novel open field. These data suggest that the absence of D₄Rs is not sufficient to cause psychopathologies associated with heightened impulsivity and novelty seeking.