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.
Highlights
Dopamine (DA) is known to be implicated in a variety of functions including reward [1, 2] and physical mobility [3, 4]
While traditional models understand DA-related locomotion through the cAMP pathway, modulated by the opposite functions of D1 and D2 receptors, it has been demonstrated that the PLC/IP3 pathway contributes to locomotion exclusively through the activation of the D1 receptor; establishing the involvement of D1 receptor function in the discussion of Parkinson’s disease (PD) [19]
Drd2 +/+ mice significantly benefited from an EE, living more than 18% longer than their deprived environment (DE) counterparts
Summary
Dopamine (DA) is known to be implicated in a variety of functions including reward [1, 2] and physical mobility [3, 4]. Several key areas of the brain are vulnerable to the effects of aging: the substantia nigra (SNc), the ventral tegmental area (VTA), and the striatum. Decline in DA neuron populations within these areas, especially within the nigrostriatal pathway, has been shown to contribute to motor impairment and the progression of Parkinson’s disease (PD) [13,14,15,16]. A D2R deficiency has been known to lead to reduced spontaneous mobility and produce PD-like symptoms [18]. It should www.impactjournals.com/oncotarget be noted that alterations in other DA receptor may play an integral role in motor output. While traditional models understand DA-related locomotion through the cAMP pathway, modulated by the opposite functions of D1 and D2 receptors, it has been demonstrated that the PLC/IP3 pathway contributes to locomotion exclusively through the activation of the D1 receptor; establishing the involvement of D1 receptor function in the discussion of PD [19]
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