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

Abstract

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.

Hedgehog Signaling Modulates Glial Proteostasis and Lifespan

“…We next decided to investigate whether the hh mutant flies exhibit any survival or behavioral deficits, because defects in the dopaminergic neuron network have been demonstrated to have a detrimental effect upon lifespan and locomotor activity in both mammals and invertebrates (Thanos et al, 2016;Liao et al, 2017;Feany and Bender, 2000). Strikingly, we found that both female and male adult hh ts flies shifted to 29 C exhibit a drastically shortened lifespan (80%-85% decrease in the median lifespan when compared to control flies) (Figures 2A and S3C; Table S2).…”

To Do or Not to Do: Dopamine, Affordability and the Economics of Opportunity

“…D2R in the striatum has been associated with the regulation of motivated, appetitive behavior, including reinforcement learning and behavioral flexibility. D2R has also been implicated in generalized behavioral activation (Tataranni et al, 2001 ; Kravitz et al, 2010 ; Klinker et al, 2013 ; Beeler et al, 2016 ; Friend et al, 2016 ; Lemos et al, 2016 ; Thanos et al, 2016 ). Each could potentially explain the other; that is, blocking D2R could reduce motivation, effectively reducing activity or, conversely, a generalized restriction on activity and energy expenditure could diminish apparent motivation.…”

Coupling Genetic Addiction Risk Score (GARS) and Pro Dopamine Regulation (KB220) to Combat Substance Use Disorder (SUD)

“…The traditionally used therapeutic agents have failed to address the reduced connectivity patterns now seen in many addictions and have had limited success in relapse prevention and effective recovery from psychoactive substance abuse [4,54]. This concept would enable genetic testing and precise treatment of genetic and epigenetic deficits with formulations of KB220 [55,56]. Recovery and good health would be the goal of this SMART, holistic program design, based on this extensive research in a diverse but stable population [57].…”