Imaging Dopamine D3 Receptors in the Human Brain with Positron Emission Tomography, [11C]PHNO, and a Selective D3 Receptor Antagonist

Searle, Graham; Beaver, John D.; Comley, Robert A.; Bani, Massimo; Tziortzi, Andri C.; Slifstein, Mark; Mugnaini, Manolo; Griffante, Cristiana; Wilson, Alan A.; Merlo‐Pich, Emilio; Houle, Sylvain; Gunn, Roger N.; Rabiner, Eugenii A.; Laruelle, Marc

doi:10.1016/j.biopsych.2010.04.038

Cited by 142 publications

(183 citation statements)

References 27 publications

Supporting

Mentioning

174

Contrasting

Order By: Relevance

“…In the present study, the highest uptake and binding potentials were in the caudate nucleus, putamen, and ventral striatum. Previous studies in humans found a similar pattern of distribution of PHNO binding, with highest binding potentials in the putamen, globus pallidus, and substantia nigra (Searle et al, 2010;Boileau et al, 2012;Gallezot et al, 2014). Tziortzi and colleagues (2011) …”

Section: Discussionmentioning

confidence: 64%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 64%

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

View full text Add to dashboard Cite

show abstract

“…We only found a significant correlation between change in compulsivity to use cannabis following the control scan and GP BP ND (r ¼ 0. Stress-induced dopamine response in cannabis users R Mizrahi et al (Narendran et al, 2006b;Rabiner et al, 2009 (Searle et al, 2010;Tziortzi et al, 2011). In other regions like the dorsal striatum (caudate, AST and putamen, SMST), the relative concentration of D 2 receptors is much higher and, therefore, only a small component of the signal, 10-40%, is attributable to D 3 (Searle et al, 2010;Tziortzi et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

“…Stress-induced dopamine response in cannabis users R Mizrahi et al (Narendran et al, 2006b;Rabiner et al, 2009 (Searle et al, 2010;Tziortzi et al, 2011). In other regions like the dorsal striatum (caudate, AST and putamen, SMST), the relative concentration of D 2 receptors is much higher and, therefore, only a small component of the signal, 10-40%, is attributable to D 3 (Searle et al, 2010;Tziortzi et al, 2011). Consequently, observed elevated BP ND suggest that chronic cannabis use may result in increased receptor availability in D 2 -rich regions (AST, LST, SMST and the whole striatum), while the D 3 -rich regions are relatively unaffected.…”

Section: Resultsmentioning

confidence: 99%

Dopamine Response to Psychosocial Stress in Chronic Cannabis Users: A PET Study With [11C]-(+)-PHNO

Mizrahi

Suridjan

Kenk

et al. 2012

Neuropsychopharmacol

Self Cite

View full text Add to dashboard Cite

A number of addictions have been linked with decreased striatal dopamine (DA) receptor availability and DA release. Stress has a key role in cannabis craving, as well as in modulation of dopaminergic signaling. The present study aimed to assess DA release in response to a laboratory stress task with [ 11 C]-( þ )-PHNO positron emission tomography in cannabis users (CU). Thirteen healthy CU and 12 healthy volunteers (HV) were scanned during a sensorimotor control task (SMCT) and under a stress condition using the validated Montreal imaging stress task (MIST). The simplified reference tissue model (SRTM) was used to obtain binding potential (BP ND ) in striatal subdivisions: limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST). Stress-induced DA release (indexed as a percentage of reduction in , with no effect in any other brain region. In conclusion, despite an increase in striatal BP ND observed during the control task, chronic cannabis use is not associated with alterations in stress-induced DA release.

show abstract

“…The D 3 -preferring D 2/3 R agonist PET tracer, [ 11 C](+) PHNO, has been found to be especially reliable (due to an excellent specific-to-nonspecific binding ratio) at quantifying extrastriatal midbrain reward regions particularly essential for the synthesis and production of dopamine such as the SN/VTA, where D 3 Rs are predominant (Graff-Guerrero et al, 2008;Narendran et al, 2006;Searle et al, 2010;Tziortzi et al, 2011). In addition, [ 11 C](+)PHNO has also been shown to bind to high-affinity, presumably 'active', G-protein coupled forms of the D 2 R within the striatum (Shotbolt et al, 2012;Willeit et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO

Gaiser

Gallezot

Worhunsky

et al. 2016

Neuropsychopharmacol

View full text Add to dashboard Cite

Most prior work with positron emission tomography (PET) dopamine subtype 2/3 receptor (D 2/3 R) non-selective antagonist tracers suggests that obese (OB) individuals exhibit lower D 2/3 Rs when compared with normal weight (NW) individuals. A D 3 -preferring D 2/3 R agonist tracer, [ 11 C](+)PHNO, has demonstrated that body mass index (BMI) was positively associated with D 2/3 R availability within striatal reward regions. To date, OB individuals have not been studied with [ 11 C](+)PHNO. We assessed D 2/3 R availability in striatal and extrastriatal reward regions in 14 OB and 14 age-and gender-matched NW individuals with [ 11 C](+)PHNO PET utilizing a high-resolution research tomograph. Additionally, in regions where group D 2/3 R differences were observed, secondary analyses of 42 individuals that constituted an overweight cohort was done to study the linear association between BMI and D 2/3 R availability in those respective regions. A group-by-brain region interaction effect (F 7, 182 = 2.08, p= 0.047) was observed. Post hoc analyses revealed that OB individuals exhibited higher tracer binding in D 3 -rich regions: the substantia nigra/ventral tegmental area (SN/VTA) (+20%; p = 0.02), ventral striatum (VST) (+14%; po0.01), and pallidum (+11%; p = 0.02). BMI was also positively associated with D 2/3 R availability in the SN/VTA (r = 0.34, p = 0.03), VST (r = 0.36, p = 0.02), and pallidum (r = 0.30, p = 0.05) across all subjects. These data suggest that individuals who are obese have higher D 2/3 R availability in brain reward regions densely populated with D 3 Rs, potentially identifying a novel pharmacologic target for the treatment of obesity.

show abstract

Imaging Dopamine D3 Receptors in the Human Brain with Positron Emission Tomography, [11C]PHNO, and a Selective D3 Receptor Antagonist

Cited by 142 publications

References 27 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

Dopamine Response to Psychosocial Stress in Chronic Cannabis Users: A PET Study With [11C]-(+)-PHNO

Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO

Contact Info

Product

Resources

About

Imaging Dopamine D3 Receptors in the Human Brain with Positron Emission Tomography, [11C]PHNO, and a Selective D3 Receptor Antagonist

Cited by 142 publications

References 27 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

Dopamine Response to Psychosocial Stress in Chronic Cannabis Users: A PET Study With [11C]-(+)-PHNO

Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO

Contact Info

Product

Resources

About

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