title: 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.
authors.affiliation: Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, USA.
authors.forename: Panayotis K
authors.initials: PK
authors.lastname: Thanos
authors.affiliation: Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hamilton
authors.affiliation: Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: O'Rourke
authors.affiliation: Department of Psychology, Suffolk Community College, Riverhead, NY, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Napoli
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Febo
authors.affiliation: NIDA, Bethesda, MD, USA.
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Blum
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Gold
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D059647:Gene-Environment Interaction; D005838:Genotype; D008136:Longevity / Q000235:genetics*; D008297:Male; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism
chemical_list: C000600618:DRD2 protein, mouse; D017448:Receptors, Dopamine D2; D004298:Dopamine
keywords: D2; Gerotarget; aging; cognition; environmental enrichment; exercise