Imaging dopamine receptors in humans with [11C]-(+)-PHNO: Dissection of D3 signal and anatomy

Tziortzi, Andri C.; Searle, Graham; Tzimopoulou, Sofia; Salinas, Cristian; Beaver, John D.; Jenkinson, Mark; Laruelle, Marc; Rabiner, Eugenii A.; Gunn, Roger N.

doi:10.1016/j.neuroimage.2010.06.044

Cited by 383 publications

(423 citation statements)

References 30 publications

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“…For example, monkeys experienced fewer yawns with increasing D3R binding potential in the ventral pallidum. This relationship is not consistent with the high D3R signal reported in that brain region (Tziortzi et al, 2011), suggesting a possible alternative mechanism. Past studies have implicated specific brain areas in dopamine agonist-elicited yawning, including the nigrostriatal pathway, hypothalamus, and the paraventricular nucleus (Dourish and Hutson, 1985;Melis et al, 1987); thus, it is expected that yawning does not necessarily have to correlate with D3R and D2R signal in every brain region.…”

Section: Discussioncontrasting

confidence: 82%

“…These investigators found that 100% of PHNO signal in the substantia nigra and hypothalamus and the majority of the signal in the ventral pallidum and globus pallidus were D3R-mediated. In contrast, only 20% of the signal in the ventral striatum was attributed to D3R, whereas 100% of the signal in the caudate nucleus was a result of D2R binding (Tziortzi et al, 2011). Because the ascending limb of the quinpirole-elicited yawning dose-response curve is thought to be D3R-mediated (Collins et al., 2005(Collins et al., , 2007, the results of the mixed model, which showed approximately five greater yawns for every 1-unit increase in binding potential in the globus pallidus, support this conclusion.…”

Section: Discussionmentioning

confidence: 86%

“…Spherical regions of interest (ROI) were drawn on individual MR images for the caudate nucleus (Cd; 2.5 mm radii), putamen (Pt; 2.5 mm radii), globus pallidus (GP; 2.5 mm radii), ventral striatum (2.0 mm radii), ventral pallidum (VP; 2.0 mm radii), thalamus (3.0 mm radii), substantia nigra (2.0 mm radii), hippocampus (HIP; 2.4 mm radii), and cerebellum (4.0 mm radii). The GP, VP, thalamus, and substantia nigra were chosen because they are rich in D3R (Tziortzi et al, 2011), the Cd, Pt, and ventral striatum were chosen because of their involvement in addiction (Koob and Volkow, 2010), and the HIP because of its role in yawning (Argiolas and Melis, 1998). For monkey #1711, the PET data were coregistered to the MRI obtained from monkey #1710 based on the similar weight and age of the two subjects.…”

Section: Experiments 1: Relationship Between D3r Availability and Quinmentioning

confidence: 99%

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Further Characterization of Quinpirole-Elicited Yawning as a Model of Dopamine D₃ Receptor Activation in Male and Female Monkeys

Martelle

Nader

Czoty

et al. 2014

J Pharmacol Exp Ther

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The dopamine (DA) D 3 receptor (D3R) has been associated with impulsivity, pathologic gambling, and drug addiction, making it a potential target for pharmacotherapy development. Positron emission tomography studies using the D3R-preferring radioligand [ 11 C]PHNO ([ 11 C](+)-propyl-hexahydro-naphtho-oxazin) have shown higher binding potentials in drug abusers compared with control subjects. Preclinical studies have examined D3R receptor activation using the DA agonist quinpirole and the unconditioned behavior of yawning. However, the relationship between quinpirole-elicited yawning and D3R receptor availability has not been determined. In Experiment 1, eight drug-naive male rhesus monkeys were scanned with [ 11 C]PHNO, and the ability of quinpirole (0.01-0.3 mg/kg i.m.) to elicit yawning was examined. Significant positive (globus pallidus) and negative (caudate nucleus, putamen, ventral pallidum, and hippocampus) relationships between D3R receptor availability and quinpirole-induced yawns were noted. Experiment 2 replicated earlier findings that a history of cocaine self-administration (n = 11) did not affect quinpirole-induced yawning and extended this to examine monkeys (n = 3) with a history of methamphetamine (MA) selfadministration and found that monkeys with experience selfadministering MA showed greater potency and significantly higher quinpirole-elicited yawning compared with controls. Finally, quinpirole-elicited yawning was studied in drug-naive female monkeys (n = 6) and compared with drug-naive male monkeys (n = 8). Sex differences were noted, with quinpirole being more potent and eliciting significantly more yawns in males compared with females. Taken together these findings support the use of quinpirole-elicited yawning as a behavioral tool for examining D3R activation in monkeys and that both drug history and sex may influence individual sensitivity to the behavioral effects of D3R compounds.

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Section: Discussioncontrasting

confidence: 82%

Section: Discussionmentioning

confidence: 86%

Section: Experiments 1: Relationship Between D3r Availability and Quinmentioning

confidence: 99%

See 1 more Smart Citation

Further Characterization of Quinpirole-Elicited Yawning as a Model of Dopamine D₃ Receptor Activation in Male and Female Monkeys

Martelle

Nader

Czoty

et al. 2014

J Pharmacol Exp Ther

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“…The CIC neuroanatomical atlas 18 was nonlinearly deformed into the individual's space, via T1 magnetic resonance imaging data mapping, to obtain a personalized anatomical parcellation of ROIs. Attention focused on regions of different levels of binding 10 are as follows: frontal, occipital, parietal, temporal, and cingulate cortex, hippocampus, thalamus, striatum, putamen, cerebellum, brainstem, midbrain, and pons.…”

Section: Image Analysismentioning

confidence: 99%

Determination of [¹¹C]PBR28 Binding Potential in vivo: A First Human TSPO Blocking Study

Owen

Guo

Kalk

et al. 2014

J Cereb Blood Flow Metab

122

133

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Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BP ND ). Here, we used blockade of the TSPO radioligand [ 11 C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (V ND ), and hence estimate the BP ND . A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [ 11 C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, V ND was estimated via the occupancy plot. Values of BP ND for all subjects were calculated using this V ND estimate. Total volume of distribution (V T ) of MABs (2.94±0.31) was lower than V T of HABs (4.33±0.29) (Po0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50 ¼ 0.34±0.13 mg/kg). The occupancy plot provided a V ND estimate of 1.98 (1.69, 2.26). Based on these V ND estimates, BP ND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [ 11 C]PBR28 V ND and hence BP ND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating V ND for TSPO targeting radioligands.

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“…We used these scans to calculate the age‐corrected binding ratios in the dorsal‐medial striatum [Vriend et al, 2014]. The ventral striatum was delineated on a canonical T1 image according to the method described by Tziortzi et al [2013]. The dorsomedial striatum (referred to as the anterior‐dorsal striatum by Vriend et al [2014]) was traced on the same coronal slices as the ventral striatum but a gap of 5 mm was left between the two ROI's to avoid spillover effects.…”

Section: Discussionmentioning

confidence: 99%

Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity

Trujillo

Gerrits

Vriend

et al. 2015

Human Brain Mapping

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ObjectiveParkinson's disease (PD) often entails impairments of executive functions, such as planning. Although widely held that these impairments arise from dopaminergic denervation of the striatum, not all executive functions are affected early on, and the underlying neural dynamics are not fully understood. In a combined longitudinal and cross‐sectional study, we investigated how planning deficits progress over time in the early stages of PD compared to matched healthy controls. We used functional magnetic resonance imaging (fMRI) to identify accompanying neural dynamics.MethodsSeventeen PD patients and 20 healthy controls performed a parametric Tower of London task at two time points separated by ∼3 years (baseline and follow‐up). We assessed task performance longitudinally in both groups; at follow‐up, a subset of participants (14 patients, 19 controls) performed a parallel version of the task during fMRI. We performed meta‐analyses to localize regions‐of‐interest (ROIs), that is, the bilateral dorsolateral prefrontal cortex (DLPFC), inferior parietal cortex, and caudate nucleus, and performed group‐by‐task analyses and within‐group regression analyses of planning‐related neural activation. We studied task‐related functional connectivity of seeds in the DLPFC and caudate nucleus.ResultsPD patients, compared with controls, showed impaired task performance at both time‐points, while both groups showed similar performance reductions from baseline to follow‐up. Compared to controls, patients showed lower planning‐related brain activation together with decreased functional connectivity.ConclusionThese findings support the notion that planning is affected early in the PD disease course, and that this impairment in planning is accompanied by decreases in both task‐related brain activity and connectivity. Hum Brain Mapp 36:3703–3715, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

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Imaging dopamine receptors in humans with [11C]-(+)-PHNO: Dissection of D3 signal and anatomy

Cited by 383 publications

References 30 publications

Further Characterization of Quinpirole-Elicited Yawning as a Model of Dopamine D₃ Receptor Activation in Male and Female Monkeys

Further Characterization of Quinpirole-Elicited Yawning as a Model of Dopamine D₃ Receptor Activation in Male and Female Monkeys

Determination of [¹¹C]PBR28 Binding Potential in vivo: A First Human TSPO Blocking Study

Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity

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Imaging dopamine receptors in humans with [11C]-(+)-PHNO: Dissection of D3 signal and anatomy

Cited by 383 publications

References 30 publications

Further Characterization of Quinpirole-Elicited Yawning as a Model of Dopamine D3 Receptor Activation in Male and Female Monkeys

Further Characterization of Quinpirole-Elicited Yawning as a Model of Dopamine D3 Receptor Activation in Male and Female Monkeys

Determination of [11C]PBR28 Binding Potential in vivo: A First Human TSPO Blocking Study

Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity

Contact Info

Product

Resources

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Further Characterization of Quinpirole-Elicited Yawning as a Model of Dopamine D₃ Receptor Activation in Male and Female Monkeys

Further Characterization of Quinpirole-Elicited Yawning as a Model of Dopamine D₃ Receptor Activation in Male and Female Monkeys

Determination of [¹¹C]PBR28 Binding Potential in vivo: A First Human TSPO Blocking Study