scholarly journals Effects of an Adenosine A2A Receptor Antagonist on Striatal Dopamine D2-Type Receptor Availability: A Randomized Control Study Using Positron Emission Tomography

2021 ◽  
Vol 15 ◽  
Author(s):  
Kyoji Okita ◽  
Koichi Kato ◽  
Yoko Shigemoto ◽  
Noriko Sato ◽  
Toshihiko Matsumoto ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Substance Use ◽  
Receptor Antagonist ◽  
Substance Use Disorders ◽  
Emission Tomography ◽  
Binding Potential ◽  
Dopamine D2 ◽  
Positron Emission ◽  
A2a Receptor ◽  
Type Receptor

Introduction: Altered dopaminergic neurotransmission, especially in the functioning of dopamine D2-type receptors, is considered central to the etiology of a variety of neuropsychiatric disorders. In particular, individuals with substance use disorders have been consistently observed to exhibit lower D2-type receptor availability (quantified as binding potential; BPND) using positron emission tomography (PET). Upregulation of D2-type receptor density thus may therefore provide a therapeutic effect for substance use disorders. Importantly, in vitro studies reveal that D2 receptors coexist with adenosine 2A (A2A) receptors to form the highest density of heteromers in the whole striatum, and there is a functional interaction between these two receptors. As such, blockade of A2A receptor’s function may prevent D2 receptor downregulation, yet no study has currently examined this hypothesis in humans.Methods and Analysis: This double-blind, randomized controlled trial aims to evaluate the effect of the A2A receptor antagonist istradefylline (compared to placebo) on both dopamine D2-type receptor availability in the human brain and on neuropsychological measurements of impulsivity. It is hypothesized that istradefylline will both increase striatal D2-type BPND and improve control of impulsivity more than placebo. Forty healthy participants, aged 20–65 with no history of psychiatric or neurological disorders, will be recruited and randomized into two groups and will undergo [11C]raclopride PET, once before and once after administration of either 40 mg/day istradefylline or placebo for 2 weeks. Neuropsychological measurements will be administered on the same days of the PET scans.Ethics and Dissemination: The study protocol was approved by the Certified Review Boards (CRB) of National Center of Neurology and Psychiatry (CR18-011) and prospectively registered with the Japan Registry of Clinical Trials (jRCTs031180131; https://jrct.niph.go.jp/latest-detail/jRCTs031180131). The findings of this study will be disseminated through peer reviewed scientific journals and conferences.Clinical Trial Registration:www.ClinicalTrials.gov, identifier jRCTs031180131.

Increased Dopamine D2/D3 Receptor Binding After Recovery from Anorexia Nervosa Measured by Positron Emission Tomography and [11C]Raclopride

2005 ◽  
Vol 58 (11) ◽  
pp. 908-912 ◽  
Author(s):  
Guido K. Frank ◽  
Ursula F. Bailer ◽  
Shannan E. Henry ◽  
Wayne Drevets ◽  
Carolyn C. Meltzer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Anorexia Nervosa ◽  
Receptor Binding ◽  
Emission Tomography ◽  
D3 Receptor ◽  
Dopamine D2 ◽  
Positron Emission

scholarly journals Effects of lowered serotonin transmission on cocaine-induced striatal dopamine response: PET [11C]raclopride study in humans

2011 ◽  
Vol 199 (5) ◽  
pp. 391-397 ◽  
Author(s):  
Sylvia M. L. Cox ◽  
Chawki Benkelfat ◽  
Alain Dagher ◽  
J. Scott Delaney ◽  
France Durand ◽  
...  
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Striatal Dopamine ◽  
Emission Tomography ◽  
Acute Tryptophan Depletion ◽  
Tryptophan Depletion ◽  
Comorbid Conditions ◽  
Drug Craving ◽  
Positron Emission ◽  
Wide Range

BackgroundLow serotonin transmission is thought to increase susceptibility to a wide range of substance use disorders and impulsive traits.AimsTo investigate the effects of lowered serotonin on cocaine-induced (1.0 mg/kg cocaine, self-administered intranasally) dopamine responses and drug craving.MethodIn non-dependent cocaine users, serotonin transmission was reduced using the acute tryptophan depletion method. Striatal dopamine responses were measured using positron emission tomography with [11C]raclopride.ResultsAcute tryptophan depletion increased drug craving and striatal dopamine responses to cocaine. These acute tryptophan depletion-induced increases did not occur in the absence of cocaine.ConclusionsThe results suggest that low serotonin transmission can increase dopaminergic and appetitive responses to cocaine. These findings might identify a mechanism by which individuals with low serotonin are at elevated risk for both substance use disorders and comorbid conditions.

Dopamine D2 and serotonin S2 receptors in susceptibility to methamphetamine psychosis detected by positron emission tomography

1993 ◽  
Vol 50 (4) ◽  
pp. 217-231 ◽  
Author(s):  
Masaomi Iyo ◽  
Masato Nishio ◽  
Takashi Itoh ◽  
Hiroshi Fukuda ◽  
Kazutoshi Suzuki ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Dopamine D2 ◽  
Positron Emission

In vivo imaging of adenovirus-mediated over-expression of dopamine D2 receptors in rat striatum by positron emission tomography

Neuroreport ◽  
2000 ◽  
Vol 11 (4) ◽  
pp. 743-748 ◽  
Author(s):  
Osamu Ogawa ◽  
Hiroyuki Umegaki ◽  
Kiichi Ishiwata ◽  
Yukako Asai ◽  
Hiroyuki Ikari ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
In Vivo Imaging ◽  
D2 Receptors ◽  
Dopamine D2 Receptors ◽  
Emission Tomography ◽  
Rat Striatum ◽  
Over Expression ◽  
Dopamine D2 ◽  
Positron Emission

A Double-Injection Technique for in vivo Measurement of Dopamine D2-Receptor Density in Monkeys with 3-(2'-[18F] Fluoroethyl)Spiperone and Dynamic Positron Emission Tomography

1989 ◽  
Vol 9 (6) ◽  
pp. 850-858 ◽  
Author(s):  
Sung-Cheng Huang ◽  
Mark M. Bahn ◽  
Jorge R. Barrio ◽  
John M. Hoffman ◽  
Nagichettiar Satyamurthy ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Emission Tomography ◽  
Injection Technique ◽  
Receptor Density ◽  
Dopamine D2 ◽  
Positron Emission ◽  
Kinetics Of

Dopamine D2-receptor density in striatum of monkey was measured with 3-(2'-[18F]fluoroethyl)spiperone (FESP) and dynamic positron emission tomography (PET), using a double-injection technique. A first bolus of high specific activity (SA) FESP (5 mCi; ≃ 1 Ci/μmol) was injected i.v.; 90 min later, a second bolus of lower SA FESP (5 mCi; ≃ 0.04 Ci/μmol) was injected. A dynamic PET study was performed to measure the kinetics of FESP in striatum over 180 min, and the metabolite-corrected concentration of FESP in plasma as a function of time was obtained from arterial blood samples. A nonlinear compartmental model that took into account the saturability of the receptor binding was used to describe the kinetics of FESP in striatum. Model parameters were estimated by regression with a constraint based on information about the equilibrium dissociation constant of the ligand–receptor binding. Dopamine D2-receptor density in striatum was estimated to be 25.9 ± 12.7 pmol/g in seven Macaca nemestrina monkeys. The method does not require the use of cerebellum as a reference tissue region and an estimate of dopamine D2-receptor density can be obtained from a single study.

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