Research Papers: Gerotarget (Focus on Aging):

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

Panayotis K. Thanos _, John Hamilton, Joseph R. O’Rourke, Anthony Napoli, Marcelo Febo, Nora D. Volkow, Kenneth Blum and Mark Gold

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Oncotarget. 2016; 7:19111-19123. https://doi.org/10.18632/oncotarget.8088

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Panayotis K. Thanos1, John Hamilton1, Joseph R. O’Rourke1, Anthony Napoli2, Marcelo Febo3, Nora D. Volkow4, Kenneth Blum3 and Mark Gold3

1 Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, USA

2 Department of Psychology, Suffolk Community College, Riverhead, NY, USA

3 Department of Psychiatry, University of Florida, Gainesville, FL, USA

4 NIDA, Bethesda, MD, USA

Correspondence to:

Panayotis K. Thanos, email:

Keywords: aging, D2, environmental enrichment, exercise, cognition, Gerotarget

Received: January 08, 2016 Accepted: February 23, 2016 Published: March 15, 2016


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.

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