Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging

Volkow, Nora D.; Wang, G. J.; Fowler, Joanna S.; Ding, Yu-Sin; Gur, Ruben C.; Gatley, John; Logan, Jean; Moberg, Paul J.; Hitzemann, Robert; Smith, G. S.; Pappas, Naomi

doi:10.1002/ana.410440125

Cited by 161 publications

(110 citation statements)

References 18 publications

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“…This is in accordance with existing in vitro and in vivo evidence of a significant decline in DRD2/3 density with age (Antonini et al, 1993;Ichise et al, 1998;Ishibashi et al, 2009;Rinne et al, 1990;Severson et al, 1982;Volkow et al, 1998;Wong et al, 1997). In addition, among our ADP, DRD3 blockade in the putamen and thalamus was negatively associated with age.…”

Section: D3 Receptors In Alcoholismsupporting

confidence: 93%

“…To explore whether PET outcome measures and other variables, such as drinking parameters, smoking parameters, and psychometric data, were related, multiple linear regression analysis with V T or D DRD3 V T (%) was included as the dependent variable. Age was also included as a covariate in these analyses as DRD2/3 levels decline with age (Antonini et al, 1993;Ichise et al, 1998;Ishibashi et al, 2009;Rinne et al, 1990;Severson et al, 1982;Volkow et al, 1998;Wong et al, 1997). To assess whether there was a significant V T blockade in the cerebellum, onetailed paired t-test for pre-vs post-blockade cerebellar V T values for each group was applied.…”

Section: Statisticsmentioning

confidence: 99%

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In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

Erritzoe

Tziortzi

Bargiela

et al. 2014

Neuropsychopharmacol

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Animal studies support the role of the dopamine D3 receptor (DRD3) in alcohol reinforcement or liking. Sustained voluntary alcohol drinking in rats has been associated with an upregulation of striatal DRD3 gene expression and selective blockade of DRD3 reduces ethanol preference, consumption, and cue-induced reinstatement. In vivo measurement of DRD3 in the living human brain has not been possible until recently owing to a lack of suitable tools. In this study, DRD3 status was assessed for the first time in human alcohol addiction. Brain DRD3 availability was compared between 16 male abstinent alcohol-dependent patients and 13 healthy non-dependent age-matched males using the DRD3-preferring agonist positron emission tomography (PET) radioligand [ 11 C]PHNO with and without blockade with a selective DRD3 antagonist (GSK598809 60 mg p.o.). In striatal regions of interest, where the [ 11 C]PHNO PET signal represents primarily DRD2 binding, no differences were seen in [ 11 C]PHNO binding between the groups at baseline. However, baseline [ 11 C]PHNO binding was higher in alcohol-dependent patients in hypothalamus (V T : 16.5±4 vs 13.7±2.9, p ¼ 0.040), a region in which the [ 11 C]PHNO signal almost entirely reflects DRD3 availability. The reductions in regional receptor binding (V T ) following a single oral dose of GSK598809 (60 mg) were consistent with those observed in previous studies across all regions. There were no differences in regional changes in V T following DRD3 blockade between the two groups, indicating that the regional fractions of DRD3 are similar in the two groups, and the increased [ 11 C]PHNO binding in the hypothalamus in alcohol-dependent patients is explained by elevated DRD3 in this group. Although we found no difference between alcohol-dependent patients and controls in striatal DRD3 levels, increased DRD3 binding in the hypothalamus of alcohol-dependent patients was observed. This may be relevant to the development of future therapeutic strategies to treat alcohol abuse.

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Section: D3 Receptors In Alcoholismsupporting

confidence: 93%

Section: Statisticsmentioning

confidence: 99%

In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

Erritzoe

Tziortzi

Bargiela

et al. 2014

Neuropsychopharmacol

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“…Thus, slow recovery of TH, DA, and 5-HT systems from METH, coupled with the age-related decline in DA and 5-HT systems in GDNF ϩ/Ϫ mice, may underlie the exacerbated motor deficits in GDNF ϩ/Ϫ mice at 12 months of age. Exacerbated reduction in the function of the nigrostriatal DA system has consistently been associated with greater decline in motor function with aging in both humans (Suhara et al, 1991;Bannon et al, 1992;Volkow et al, 1998) and animals (Emborg et al, 1998;Hebert and Gerhardt, 1998;Cass et al, 2005;Yurek and Fletcher-Turner, 2001). …”

Section: Gdnfmentioning

confidence: 99%

Long-Term Consequences of Methamphetamine Exposure in Young Adults Are Exacerbated in Glial Cell Line-Derived Neurotrophic Factor Heterozygous Mice

Boger¹,

Middaugh²,

Patrick³

et al. 2007

J. Neurosci.

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Methamphetamine abuse in young adults has long-term deleterious effects on brain function that are associated with damage to monoaminergic neurons. Administration of glial cell line-derived neurotrophic factor (GDNF) protects dopamine neurons from the toxic effects of methamphetamine in animal models. Therefore, we hypothesized that a partial GDNF gene deletion would increase the susceptibility of mice to methamphetamine neurotoxicity during young adulthood and possibly increase age-related deterioration of behavior and dopamine function. Two weeks after a methamphetamine binge (4 ϫ 10 mg/kg, i.p., at 2 h intervals), GDNF ϩ/Ϫ mice had a significantly greater reduction of tyrosine hydroxylase immunoreactivity in the medial striatum, a proportionally greater depletion of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the striatum, and a greater increase in activated microglia in the substantia nigra than wild-type mice. At 12 months of age, methamphetamine-treated GDNF ϩ/Ϫ mice exhibited less motor activity and lower levels of tyrosine hydroxylase-immunoreactivity, dopamine, DOPAC, and serotonin than wild-type mice. Greater striatal dopamine transporter activity in GDNF ϩ/Ϫ mice may underlie their differential response to methamphetamine. These data suggest the possibility that methamphetamine use in young adults, when combined with lower levels of GDNF throughout life, may precipitate the appearance of parkinsonian-like behaviors during aging.

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“…It is well established that various aspects of dopaminergic modulation decline substantially during the course of usual aging (see Bäckman et al, 2000;Volkow et al, 1998;see Bäckman, Nyberg, Lindenberger, Li, & Farde, 2006 for recent review). Using the same experimental paradigm, we recently have shown that older adults, relative to younger adults, are less able to focus their attention on the attended ear; rather, their performance is primarily driven by the perceptual saliency of the auditory inputs (Passow et al, 2012a).…”

Section: Effects Of Dopamine Genes On Attentional Agingmentioning

confidence: 99%

Dopamine modulates attentional control of auditory perception: DARPP-32 (PPP1R1B) genotype effects on behavior and cortical evoked potentials

Passow

Nietfeld

et al. 2013

Neuropsychologia

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a b s t r a c tUsing a specific variant of the dichotic listening paradigm, we studied the influence of dopamine on attentional modulation of auditory perception by assessing effects of allelic variation of a single-nucleotide polymorphism (SNP) rs907094 in the DARPP-32 gene (dopamine and adenosine 3′, 5′-monophosphateregulated phosphoprotein 32 kilodations; also known as PPP1R1B) on behavior and cortical evoked potentials. A frequent DARPP-32 haplotype that includes the A allele of this SNP is associated with higher mRNA expression of DARPP-32 protein isoforms, striatal dopamine receptor function, and frontal-striatal connectivity. As we hypothesized, behaviorally the A homozygotes were more flexible in selectively attending to auditory inputs than any G carriers. Moreover, this genotype also affected auditory evoked cortical potentials that reflect early sensory and late attentional processes. Specifically, analyses of eventrelated potentials (ERPs) revealed that amplitudes of an early component of sensory selection (N1) and a late component (N450) reflecting attentional deployment for conflict resolution were larger in A homozygotes than in any G carriers. Taken together, our data lend support for dopamine's role in modulating auditory attention both during the early sensory selection and late conflict resolution stages.

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Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging

Cited by 161 publications

References 18 publications

In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

Long-Term Consequences of Methamphetamine Exposure in Young Adults Are Exacerbated in Glial Cell Line-Derived Neurotrophic Factor Heterozygous Mice

Dopamine modulates attentional control of auditory perception: DARPP-32 (PPP1R1B) genotype effects on behavior and cortical evoked potentials

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