Dopamine D₂ gene expression interacts with environmental enrichment to impact lifespan and behavior

Aging produces cellular, molecular, and behavioral changes affecting many areas of the brain. The dopamine (DA) system is known to be vulnerable to the effects of aging, which regulate behavioral functions such as locomotor activity, body weight, and reward and cognition. In particular, age-related DA D₂ receptor (D2R) changes have been of particular interest given its relationship with addiction and other rewarding behavioral properties. Male and female wild-type (Drd₂ +/+), heterozygous (Drd₂ +/-) and knockout (Drd₂ -/-) mice were reared post-weaning in either an enriched environment (EE) or a deprived environment (DE). Over the course of their lifespan, body weight and locomotor activity was assessed. While an EE was generally found to be correlated with longer lifespan, these increases were only found in mice with normal or decreased expression of the D₂ gene. Drd₂ +/+ EE mice lived nearly 16% longer than their DE counterparts. Drd₂ +/+ and Drd₂ +/- EE mice lived 22% and 21% longer than Drd₂ -/- EE mice, respectively. Moreover, both body weight and locomotor activity were moderated by environmental factors. In addition, EE mice show greater behavioral variability between genotypes compared to DE mice with respect to body weight and locomotor activity.