Ageing and the nigrostriatal dopaminergic system

Reeves, Suzanne; Bench, C. J.; Howard, Robert

doi:10.1002/gps.606

Cited by 113 publications

(88 citation statements)

References 126 publications

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“…While we covaried for age in all our analyses, we also explicitly tested for age-related effects given the extensive literature documenting age-related alterations in DA neurotransmission. 41 We found neither a main effect of age (F(21,88) = 0.948, P = 0.534) nor any age Â genotype interactions (all P-values > 0.1) on reward-related VS reactivity. Moreover, all patterns of genotype-modulated reward-related VS reactivity were similar when the analyses were restricted to subjects 45 years and younger (N = 44) or subjects 46 years and older (N = 45).…”

Section: Allele and Genotype Frequenciescontrasting

confidence: 56%

Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity

et al. 2007

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Individual differences in traits such as impulsivity involve high reward sensitivity and are associated with risk for substance use disorders. The ventral striatum (VS) has been widely implicated in reward processing, and individual differences in its function are linked to these disorders. Dopamine (DA) plays a critical role in reward processing and is a potent neuromodulator of VS reactivity. Moreover, altered DA signaling has been associated with normal and pathological reward-related behaviors. Functional polymorphisms in DA-related genes represent an important source of variability in DA function that may subsequently impact VS reactivity and associated reward-related behaviors. Using an imaging genetics approach, we examined the modulatory effects of common, putatively functional DA-related polymorphisms on reward-related VS reactivity associated with self-reported impulsivity. Genetic variants associated with relatively increased striatal DA release (DRD2 À141C deletion) and availability (DAT1 9-repeat), as well as diminished inhibitory postsynaptic DA effects (DRD2 À141C deletion and DRD4 7-repeat), predicted 9-12% of the interindividual variability in reward-related VS reactivity. In contrast, genetic variation directly affecting DA signaling only in the prefrontal cortex (COMT Val158Met) was not associated with variability in VS reactivity. Our results highlight an important role for genetic polymorphisms affecting striatal DA neurotransmission in mediating interindividual differences in reward-related VS reactivity. They further suggest that altered VS reactivity may represent a key neurobiological pathway through which these polymorphisms contribute to variability in behavioral impulsivity and related risk for substance use disorders.

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Section: Allele and Genotype Frequenciescontrasting

confidence: 56%

Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity

et al. 2007

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“…Combined declines in cognitive and motor processes with age could be due to declining dopaminergic function. Indeed, the nigrostriatal dopaminergic system plays a major role in the control of both cognitive and motor processes (Nieoullon and Coquerel 2003), and its deterioration with aging has been implicated in an array of cognitive (Arnsten and Goldman-Rakic 1985;Arnsten et al 1994;Moore et al 2005;Reeves 2005;Reeves et al 2002) and motor deficits (Emborg and Kordower 2002;Grondin et al 2000;Irwin et al 1994). Volkow et al (1998) provided support for this hypothesis, by showing that D2 receptor availability in the caudate and putamen in healthy elderly subjects was positively correlated with performance on a finger tapping task and performance on specific cognitive tasks dependent on frontal function.…”

Section: Introductionmentioning

confidence: 99%

Relationships among cognitive function, fine motor speed and age in the rhesus monkey

Lacreuse

Espinosa

Herndon

2006

AGE

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Declines in fine motor skills and cognitive function are well known features of human aging. Yet, the relationship between age-related impairments in motor and cognitive function remains unclear. Rhesus monkeys, like humans, show marked decline in cognitive and fine motor function with age and are excellent models to investigate potential interactions between age-related declines in cognitive and motor functioning. We investigated the relationships among cognition, motor function and age in 30 male and female rhesus monkeys, 5-28 years of age, tested on a battery of cognitive tasks [acquisition of the delayed non-matching-to-sample (DNMS), DNMS-120s, DNMS-600s, acquisition of delayed recognition span test (DRST), spatial-DRST and object-DRST] and a fine motor task (Lifesaver test). Global cognitive ability, as assessed by the cognitive performance index (CPI), was impaired with age in both sexes, while age-related motor slowing was found only in males. After age was controlled for, half the variance in CPI was predicted by motor speed, with better cognitive ability associated with slower motor skills. Analyses at the level of each cognitive task revealed that motor speed and age predicted the rate of acquisition of the DNMS. This relationship was robust in males and absent in females. Motor speed was not a significant predictor of any other cognitive variable. We conclude that the relationship between cognition and motor function (1) may be limited to non-spatial tasks; (2) exists independently of age; (3) may reflect different contributions of the fronto-striatal system; (4) may be particularly evident in males.

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“…As to the latter, although most studies have found a negative linear relationship between adult age and DA (see Reeves et al, 2002, for a review), some research indicates a curvilinear trajectory, with accelerated losses from young-old to very-old age (Rinne et al, 1990;Antonini et al, 1993;Bannon and Whitty, 1997;Ma et al, 1999).…”

mentioning

confidence: 99%

Linking cognitive aging to alterations in dopamine neurotransmitter functioning: Recent data and future avenues

Bäckman

Lindenberger

et al. 2010

Neuroscience & Biobehavioral Reviews

365

284

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Ageing and the nigrostriatal dopaminergic system

Cited by 113 publications

References 126 publications

Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity

Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity

Relationships among cognitive function, fine motor speed and age in the rhesus monkey

Linking cognitive aging to alterations in dopamine neurotransmitter functioning: Recent data and future avenues

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