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.

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.

scholarly journals Closing the gap between training needs and training provision in addiction medicine

2019 ◽  
Vol 17 (2) ◽  
pp. 37-39
Author(s):  
Sidharth Arya ◽  
Mirjana Delic ◽  
Blanca Iciar Indave Ruiz ◽  
Jan Klimas ◽  
Duccio Papanti ◽  
...  
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Training Needs ◽  
Addiction Medicine ◽  
Effective Interventions ◽  
Sufficient Detail ◽  
Core Set ◽  
Wide Range ◽  
Closing The Gap ◽  
And Training

Substance use disorders pose a significant global social and economic burden. Although effective interventions exist, treatment coverage remains limited. The lack of an adequately trained workforce is one of the prominent reasons. Recent initiatives have been taken worldwide to improve training, but further efforts are required to build curricula that are internationally applicable. We believe that the training needs of professionals in the area have not yet been explored in sufficient detail. We propose that a peer-led survey to assess those needs, using a standardised structured tool, would help to overcome this deficiency. The findings from such a survey could be used to develop a core set of competencies which is sufficiently flexible in its implementation to address the specific needs of the wide range of professionals working in addiction medicine worldwide.

Young Adult Outcome of Attention Deficit Hyperactivity Disorder

2016 ◽  
Author(s):  
Mai Uchida ◽  
Joseph Biederman
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Substance Use ◽  
Psychiatric Disorders ◽  
Substance Use Disorders ◽  
Attention Deficit ◽  
Massachusetts General Hospital ◽  
Emotional Dysregulation ◽  
Neural Basis ◽  
Hyperactivity Disorder ◽  
Wide Range

The Massachusetts General Hospital (MGH) Longitudinal Studies of Attention Deficit Hyperactivity Disorder (ADHD) evaluated and followed a large sample of both boys and girls with ADHD and controls without ADHD, along with their families, ascertained from psychiatric and pediatric sources. These studies documented that ADHD in both sexes is associated with high levels of persistence onto adulthood; high levels of familiality with ADHD and other psychiatric disorders; a wide range of comorbid psychiatric and cognitive disorders including mood, anxiety, and substance use disorders; learning disabilities with reading and math; executive function deficits; emotional dysregulation and autistic traits; as well as educational, social, and occupational dysfunctions. The MGH studies also suggested that stimulant treatment significantly decreased the risk of developing comorbid psychiatric disorders, substance use disorders, and impaired functional outcomes. The studies also documented the neural basis of the persistence of ADHD using resting-state functional magnetic resonance imaging (fMRI).

scholarly journals Direct arene C–H fluorination with 18F− via organic photoredox catalysis

Science ◽  
2019 ◽  
Vol 364 (6446) ◽  
pp. 1170-1174 ◽  
Author(s):  
Wei Chen ◽  
Zeng Huang ◽  
Nicholas E. S. Tay ◽  
Benjamin Giglio ◽  
Mengzhe Wang ◽  
...  
Keyword(s):  
Pharmaceutical Compounds ◽  
Emission Tomography ◽  
Light Illumination ◽  
Photoredox Catalysis ◽  
Tracer Studies ◽  
Drug Discovery And Development ◽  
Positron Emission ◽  
Wide Range ◽  
Diagnostic Agents

Positron emission tomography (PET) plays key roles in drug discovery and development, as well as medical imaging. However, there is a dearth of efficient and simple radiolabeling methods for aromatic C–H bonds, which limits advancements in PET radiotracer development. Here, we disclose a mild method for the fluorine-18 (18F)–fluorination of aromatic C–H bonds by an [18F]F− salt via organic photoredox catalysis under blue light illumination. This strategy was applied to the synthesis of a wide range of 18F-labeled arenes and heteroaromatics, including pharmaceutical compounds. These products can serve as diagnostic agents or provide key information about the in vivo fate of the labeled substrates, as showcased in preliminary tracer studies in mice.

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