Effect of Age on D2 Dopamine Receptors in Normal Human Brain Measured by Positron Emission Tomography and 11C-Raclopride

Antonini, Angelo; Leenders, Klaus L.; Reist, H.W.; Thomann, Reinhold; Beer, H.‐F.; Locher, J. T.

doi:10.1001/archneur.1993.00540050026010

Cited by 190 publications

(126 citation statements)

References 38 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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“…Autopsy studies indicate losses of both D 1 (Cortes et al, 1989;Rinne et al, 1990) and D 2 (Seeman et al, 1987;Severson et al, 1982) receptor densities from early to later adulthood, the rate of decline being estimated to just below 10% per decade. Similar findings for D 1 (Suhara et al, 1991;Wang et al, 1998) and D 2 (Nordstro¨m et al, 1992;Antonini et al, 1993;Ichise et al, 1998) receptor densities have been documented in vivo, using molecular imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT).…”

Section: Aging and Dasupporting

confidence: 56%

“…Although most studies have reported evidence for a linear age-DA relationship (see Reeves et al, 2002, for review), an exponential age trajectory with exacerbated loss after middle adulthood has been observed for both D 2 receptor densities (Rinne et al, 1990;Antonini et al, 1993) and DAT binding potential (Bannon and Whitty, 1997;Ma et al, 1999). Obviously, the latter trajectory concurs with observations of a later onset of age-related cognitive decline (Ro¨nnlund et al, 2005).…”

Section: Aging and Damentioning

confidence: 65%

The correlative triad among aging, dopamine, and cognition: Current status and future prospects

Bäckman

Nyberg

Lindenberger

et al. 2006

Neuroscience & Biobehavioral Reviews

706

563

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The brain neuronal systems defined by the neurotransmitter dopamine (DA) have since long a recognized role in the regulation of motor functions. More recently, converging evidence from patient studies, animal research, pharmacological intervention, and molecular genetics indicates that DA is critically implicated also in higher-order cognitive functioning. Many cognitive functions and multiple markers of striatal and extrastriatal DA systems decline across adulthood and aging. Research examining the correlative triad among adult age, DA, and cognition has found strong support for the view that age-related DA losses are associated with age-related cognitive deficits. Future research strategies for examining the DA-cognitive aging link include assessing (a) the generality/specificity of the effects; (b) the relationship between neuromodulation and functional brain activation; and (c) the release of DA during actual task performance. r

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“…Therefore, 5HT 1A receptors are believed to fundamentally modulate cortical excitation. (Wang et al, 1998) and D 2 (Farde et al, 1995;Antonini and Leenders, 1993), histamine H 1 (Yanai et al, 1992) and serotonin 5HT 2A (Adams et al, 2004;Meltzer et al, 1998;Sheline et al, 2002) demonstrate agedependent decline of the availability of receptors of the order of 10% pr decade. Transporters of dopamine (van Dyck et al, 2002) and serotonin (Yamamoto et al, 2002) also tend to decline with age.…”

Section: Discussionmentioning

confidence: 95%

Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

Møller

Jakobsen

Gjedde

2007

Neuropsychopharmacol

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(Gjedde, 2003;Rosa-Neto et al, 2004), which extrapolates measures of specific binding to an estimated steady-state. We compared these estimates in the two age groups with results obtained with the conventional Logan Plot and Simplified Reference Tissue Method (SRTM) applied to both regions of interestbased as parametric analyses. The regional distribution of specific binding of free sites [ 11 C]WAY-100635 was similar to that reported in previous studies, with the highest pBs in limbic structures and the raphé nuclei. Although the results of the three methods differed, pBs in the elderly subjects consistently were lower than those of young subjects. Thus, the correlation between pB and age applied to regionsof-interest revealed significant decline of pB at the rate of 3 or 4% per decade, and a 10% decline of the global mean 5HT 1A receptor-pB in elderly relative to young subjects. The results demonstrate that the number of available 5HT 1A -binding sites declines with age.

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Effect of Age on D2 Dopamine Receptors in Normal Human Brain Measured by Positron Emission Tomography and 11C-Raclopride

Cited by 190 publications

References 38 publications

In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

The correlative triad among aging, dopamine, and cognition: Current status and future prospects

Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

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