15 results on '"Watson, Ben J."'
Search Results
2. Striatal dopamine D2/D3 receptor binding in pathological gambling is correlated with mood-related impulsivity
- Author
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Clark, Luke, Stokes, Paul R., Wu, Kit, Michalczuk, Rosanna, Benecke, Aaf, Watson, Ben J., Egerton, Alice, Piccini, Paola, Nutt, David J., Bowden-Jones, Henrietta, and Lingford-Hughes, Anne R.
- Published
- 2012
- Full Text
- View/download PDF
3. Investigating expectation and reward in human opioid addiction with [11C]raclopride PET
- Author
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Watson, Ben J., Taylor, Lindsay G., Reid, Alastair G., Wilson, Sue J., Stokes, Paul R., Brooks, David J., Myers, James F., Turkheimer, Federico E., Nutt, David J., and Lingford-Hughes, Anne R.
- Published
- 2014
- Full Text
- View/download PDF
4. Acute increases in synaptic GABA detectable in the living human brain: A [11C]Ro15-4513 PET study
- Author
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Stokes, Paul R.A., Myers, Jim F., Kalk, Nicola J., Watson, Ben J., Erritzoe, David, Wilson, Sue J., Cunningham, Vincent J., Barros, Daniela Riano, Hammers, Alexander, Turkheimer, Federico E., Nutt, David J., and Lingford-Hughes, Anne R.
- Published
- 2014
- Full Text
- View/download PDF
5. Characterisation of the Contribution of the GABA-Benzodiazepine α1 Receptor Subtype to [11C]Ro15-4513 PET Images
- Author
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Myers, James FM, Rosso, Lula, Watson, Ben J, Wilson, Sue J, Kalk, Nicola J, Clementi, Nicoletta, Brooks, David J, Nutt, David J, Turkheimer, Federico E, and Lingford-Hughes, Anne R
- Published
- 2012
- Full Text
- View/download PDF
6. Acute increases in synaptic GABA detectable in the living human brain:A [¹¹C]Ro15-4513 PET study
- Author
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Stokes, Paul R A, Myers, Jim F, Kalk, Nicola J, Watson, Ben J, Erritzoe, David, Wilson, Sue J, Cunningham, Vincent J, Riano Barros, Daniela, Hammers, Alexander, Turkheimer, Federico E, Nutt, David J, and Lingford-Hughes, Anne R
- Abstract
The inhibitory γ-aminobutyric acid (GABA) neurotransmitter system is associated with the regulation of normal cognitive functions and dysregulation has been reported in a number of neuropsychiatric disorders including anxiety disorders, schizophrenia and addictions. Investigating the role of GABA in both health and disease has been constrained by difficulties in measuring acute changes in synaptic GABA using neurochemical imaging. The aim of this study was to investigate whether acute increases in synaptic GABA are detectable in the living human brain using the inverse agonist GABA-benzodiazepine receptor (GABA-BZR) positron emission tomography (PET) tracer, [(11)C]Ro15-4513. We examined the effect of 15 mg oral tiagabine, which increases synaptic GABA by inhibiting the GAT1 GABA uptake transporter, on [(11)C]Ro15-4513 binding in 12 male participants using a paired, double blind, placebo-controlled protocol. Spectral analysis was used to examine synaptic α1 and extrasynaptic α5 GABA-BZR subtype availability in brain regions with high levels of [(11)C]Ro15-4513 binding. We also examined the test-retest reliability of α1 and a5-specific [(11)C]Ro15-4513 binding in a separate cohort of 4 participants using the same spectral analysis protocol. Tiagabine administration produced significant reductions in hippocampal, parahippocampal, amygdala and anterior cingulate synaptic α1 [(11)C]Ro15-4513 binding, and a trend significance reduction in the nucleus accumbens. These reductions were greater than test-retest reliability, indicating that they are not the result of chance observations. Our results suggest that acute increases in endogenous synaptic GABA are detectable in the living human brain using [(11)C]Ro15-4513 PET. These findings have potentially major implications for the investigation of GABA function in brain disorders and in the development of new treatments targeting this neurotransmitter system.
- Published
- 2014
7. Investigating expectation and reward in human opioid addiction with [ 11 C ]raclopride PET
- Author
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Watson, Ben J., primary, Taylor, Lindsay G., additional, Reid, Alastair G., additional, Wilson, Sue J., additional, Stokes, Paul R., additional, Brooks, David J., additional, Myers, James F., additional, Turkheimer, Federico E., additional, Nutt, David J., additional, and Lingford‐Hughes, Anne R., additional
- Published
- 2013
- Full Text
- View/download PDF
8. The effects of zolpidem on in vivo binding of [C11]-flumazenil and [C11]-Ro15-4513
- Author
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Myers, Jim F.M., primary, Rosso, Lula, additional, Kalk, Nicola J., additional, Watson, Ben J., additional, Wilson, Sue, additional, Brooks, David J., additional, Nutt, David J., additional, Turkheimer, Federico E., additional, and Lingford-Hughes, Anne R., additional
- Published
- 2010
- Full Text
- View/download PDF
9. Investigating expectation and reward in human opioid addiction with [(11) C]raclopride PET.
- Author
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Watson, Ben J, Taylor, Lindsay G, Reid, Alastair G, Wilson, Sue J, Stokes, Paul R, Brooks, David J, Myers, James F, Turkheimer, Federico E, Nutt, David J, and Lingford-Hughes, Anne R
- Subjects
- *
SUBSTANCE abuse & psychology , *ANALGESICS , *BASAL ganglia , *BENZAMIDE , *BUPRENORPHINE , *DOPAMINE , *DOPAMINE antagonists , *METHADONE hydrochloride , *NARCOTICS , *RESEARCH funding , *REWARD (Psychology) , *SUBSTANCE abuse , *THOUGHT & thinking , *POSITRON emission tomography , *SUBSTANCE abuse treatment , *PHARMACODYNAMICS - Abstract
The rewarding properties of some abused drugs are thought to reside in their ability to increase striatal dopamine levels. Similar increases have been shown in response to expectation of a positive drug effect. The actions of opioid drugs on striatal dopamine release are less well characterized. We examined whether heroin and the expectation of heroin reward increases striatal dopamine levels in human opioid addiction. Ten opioid-dependent participants maintained on either methadone or buprenorphine underwent [(11) C]raclopride positron emission tomography imaging. Opioid-dependent participants were scanned three times, receiving reward from 50-mg intravenous heroin (diamorphine; pharmaceutical heroin) during the first scan to generate expectation of the same reward at the second scan, during which they only received 0.1-mg intravenous heroin. There was no heroin injection during the third scan. Intravenous 50-mg heroin during the first scan induced pronounced effects leading to high levels of expectation at the second scan. There was no detectable increase in striatal dopamine levels to either heroin reward or expectation of reward. We believe this is the first human study to examine whether expectation of heroin reward increases striatal dopamine levels in opioid addiction. The absence of detectable increased dopamine levels to both the expectation and delivery of a heroin-related reward may have been due to the impact of substitute medication. It does however contrast with the changes seen in abstinent stimulant users, suggesting that striatal dopamine release alone may not play such a pivotal role in opioid-maintained individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
10. Investigating expectation and reward in human opioid addiction with [11 C]raclopride PET.
- Author
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Watson, Ben J., Taylor, Lindsay G., Reid, Alastair G., Wilson, Sue J., Stokes, Paul R., Brooks, David J., Myers, James F., Turkheimer, Federico E., Nutt, David J., and Lingford‐Hughes, Anne R.
- Subjects
- *
OPIOID abuse , *STIMULANTS , *DRUG efficacy , *DOPAMINE , *HEROIN , *POSITRON emission tomography - Abstract
The rewarding properties of some abused drugs are thought to reside in their ability to increase striatal dopamine levels. Similar increases have been shown in response to expectation of a positive drug effect. The actions of opioid drugs on striatal dopamine release are less well characterized. We examined whether heroin and the expectation of heroin reward increases striatal dopamine levels in human opioid addiction. Ten opioid-dependent participants maintained on either methadone or buprenorphine underwent [11 C]raclopride positron emission tomography imaging. Opioid-dependent participants were scanned three times, receiving reward from 50-mg intravenous heroin (diamorphine; pharmaceutical heroin) during the first scan to generate expectation of the same reward at the second scan, during which they only received 0.1-mg intravenous heroin. There was no heroin injection during the third scan. Intravenous 50-mg heroin during the first scan induced pronounced effects leading to high levels of expectation at the second scan. There was no detectable increase in striatal dopamine levels to either heroin reward or expectation of reward. We believe this is the first human study to examine whether expectation of heroin reward increases striatal dopamine levels in opioid addiction. The absence of detectable increased dopamine levels to both the expectation and delivery of a heroin-related reward may have been due to the impact of substitute medication. It does however contrast with the changes seen in abstinent stimulant users, suggesting that striatal dopamine release alone may not play such a pivotal role in opioid-maintained individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
11. Characterisation of the contribution of the GABA-benzodiazepine α1 receptor subtype to [11C]Ro15-4513 PET images.
- Author
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Myers, James FM, Rosso, Lula, Watson, Ben J, Wilson, Sue J, Kalk, Nicola J, Clementi, Nicoletta, Brooks, David J, Nutt, David J, Turkheimer, Federico E, and Lingford-Hughes, Anne R
- Subjects
BENZODIAZEPINE receptors ,POSITRON emission tomography ,ZOLPIDEM ,GABA agonists ,BENZODIAZEPINE agonists ,FLUMAZENIL - Abstract
This positron emission tomography (PET) study aimed to further define selectivity of [
11 C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [11 C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [11 C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [11 C]Ro15-4513 time-activity curves was used to describe distribution volume (VT ) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that zolpidem caused a significant VT decrease (∼10%) in [11 C]flumazenil, but no decrease in [11 C]Ro15-4513 binding. Further analysis of [11 C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean±s.d.: 71%±41%), presumed to reflect α1-subtype binding, but not another (13%±22%), presumed to reflect α5. The proposed method for [11 C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands. [ABSTRACT FROM AUTHOR]- Published
- 2012
- Full Text
- View/download PDF
12. Acute increases in synaptic GABA detectable in the living human brain: A [11C]Ro15-4513 PET study.
- Author
-
Stokes, Paul R.A., Myers, Jim F., Kalk, Nicola J., Watson, Ben J., Erritzoe, David, Wilson, Sue J., Cunningham, Vincent J., Barros, Daniela Riano, Hammers, Alexander, Turkheimer, Federico E., Nutt, David J., and Lingford-Hughes, Anne R.
- Subjects
- *
GABA , *BRAIN imaging , *NEUROTRANSMITTERS , *COGNITIVE ability , *NEUROBEHAVIORAL disorders , *NEUROCHEMISTRY - Abstract
The inhibitory γ-aminobutyric acid (GABA) neurotransmitter system is associated with the regulation of normal cognitive functions and dysregulation has been reported in a number of neuropsychiatric disorders including anxiety disorders, schizophrenia and addictions. Investigating the role of GABA in both health and disease has been constrained by difficulties in measuring acute changes in synaptic GABA using neurochemical imaging. The aim of this study was to investigate whether acute increases in synaptic GABA are detectable in the living human brain using the inverse agonist GABA-benzodiazepine receptor (GABA-BZR) positron emission tomography (PET) tracer, [11C]Ro15-4513. We examined the effect of 15mg oral tiagabine, which increases synaptic GABA by inhibiting the GAT1 GABA uptake transporter, on [11C]Ro15-4513 binding in 12 male participants using a paired, double blind, placebo-controlled protocol. Spectral analysis was used to examine synaptic α1 and extrasynaptic α5 GABA-BZR subtype availability in brain regions with high levels of [11C]Ro15-4513 binding. We also examined the test-retest reliability of α1 and a5-specific [11C]Ro15-4513 binding in a separate cohort of 4 participants using the same spectral analysis protocol. Tiagabine administration produced significant reductions in hippocampal, parahippocampal, amygdala and anterior cingulate synaptic α1 [11C]Ro15-4513 binding, and a trend significance reduction in the nucleus accumbens. These reductions were greater than test-retest reliability, indicating that they are not the result of chance observations. Our results suggest that acute increases in endogenous synaptic GABA are detectable in the living human brain using [11C]Ro15-4513 PET. These findings have potentially major implications for the investigation of GABA function in brain disorders and in the development of new treatments targeting this neurotransmitter system. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
13. History of cigarette smoking is associated with higher limbic GABAA receptor availability
- Author
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Stokes, Paul R.A., Benecke, Aaf, Myers, Jim, Erritzoe, David, Watson, Ben J., Kalk, Nicola, Barros, Daniela Riano, Hammers, Alexander, Nutt, David J., and Lingford-Hughes, Anne R.
- Subjects
- *
GABA receptors , *PHYSIOLOGICAL effects of tobacco , *NEUROBIOLOGY , *AMYGDALOID body , *NUCLEUS accumbens , *POSITRON emission tomography - Abstract
Abstract: Cigarette smoking presents a significant worldwide healthcare challenge. Preclinical, genetic association and clinical trials studies provide considerable evidence for the involvement of the human γ-aminobutyric acid (GABA) system in the neurobiology of nicotine addiction. However there are few human GABA neurochemical imaging studies of nicotine addiction. We investigated limbic GABAA receptor availability in volunteers with a history of cigarette smoking using [11C]Ro15 4513 positron emission tomography (PET). Eight [11C]Ro15 4513 PET scans from volunteers with a history of cigarette smoking were compared to twelve scans from volunteers who were non-smokers. Total, α1 and α5 GABAA receptor subtype [11C]Ro15 4513 VT values were quantified using spectral analysis of limbic regions implicated in nicotine addiction. Spectral analysis allows quantification of the overall [11C]Ro15 4513 spectral frequency as well as α1 and α5 GABAA receptor subtype specific spectral frequency components. Volunteers with a history of cigarette smoking showed significantly higher total [11C]Ro15 4513 VT values in the presubgenual cingulate and parahippocampal gyrus, and at a trend level in the insula, nucleus accumbens and subgenual cingulate. In six abstinent previous smokers (‘ex-smokers’), total [11C]Ro15 4513 binding was significantly higher in all limbic regions studied, with higher α5 availability in the amygdala, anterior cingulate, nucleus accumbens and presubgenual cingulate. These results suggest that limbic GABAA receptor availability is higher in volunteers with a history of cigarette smoking which may reflect either higher expression of GABAA receptors or lower endogenous GABA levels. The findings in ex-smokers suggest that higher GABAA receptor availability continues with abstinence indicating that this may be a trait marker for nicotine addiction or that alterations in GABA function associated with cigarette smoking persist. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
14. Striatal dopamine D2/D3 receptor binding in pathological gambling is correlated with mood-related impulsivity
- Author
-
Clark, Luke, Stokes, Paul R., Wu, Kit, Michalczuk, Rosanna, Benecke, Aaf, Watson, Ben J., Egerton, Alice, Piccini, Paola, Nutt, David J., Bowden-Jones, Henrietta, and Lingford-Hughes, Anne R.
- Subjects
- *
DOPAMINE receptors , *MOOD (Psychology) , *COMPULSIVE gambling , *IMPULSE (Psychology) , *POSITRON emission tomography , *DRUG addiction - Abstract
Abstract: Pathological gambling (PG) is a behavioural addiction associated with elevated impulsivity and suspected dopamine dysregulation. Reduced striatal dopamine D2/D3 receptor availability has been reported in drug addiction, and may constitute a premorbid vulnerability marker for addictive disorders. The aim of the present study was to assess striatal dopamine D2/D3 receptor availability in PG, and its association with trait impulsivity. Males with PG (n=9) and male healthy controls (n=9) underwent [11C]-raclopride positron emission tomography imaging and completed the UPPS-P impulsivity scale. There was no significant difference between groups in striatal dopamine D2/D3 receptor availability, in contrast to previous reports in drug addiction. However, mood-related impulsivity (‘Urgency’) was negatively correlated with [11C]-raclopride binding potentials in the PG group. The absence of a group difference in striatal dopamine binding implies a distinction between behavioural addictions and drug addictions. Nevertheless, our data indicate heterogeneity in dopamine receptor availability in disordered gambling, such that individuals with high mood-related impulsivity may show differential benefits from dopamine-based medications. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
15. Acute increases in synaptic GABA detectable in the living human brain: a [¹¹C]Ro15-4513 PET study.
- Author
-
Stokes PR, Myers JF, Kalk NJ, Watson BJ, Erritzoe D, Wilson SJ, Cunningham VJ, Riano Barros D, Hammers A, Turkheimer FE, Nutt DJ, and Lingford-Hughes AR
- Subjects
- Adult, Dose-Response Relationship, Drug, Double-Blind Method, GABA Agonists pharmacology, Humans, Male, Memory drug effects, Middle Aged, Nipecotic Acids pharmacology, Positron-Emission Tomography, Psychomotor Performance drug effects, Receptors, GABA-A metabolism, Tiagabine, Azides, Benzodiazepines, Brain diagnostic imaging, Brain Chemistry drug effects, Radiopharmaceuticals, Synapses metabolism, gamma-Aminobutyric Acid metabolism
- Abstract
The inhibitory γ-aminobutyric acid (GABA) neurotransmitter system is associated with the regulation of normal cognitive functions and dysregulation has been reported in a number of neuropsychiatric disorders including anxiety disorders, schizophrenia and addictions. Investigating the role of GABA in both health and disease has been constrained by difficulties in measuring acute changes in synaptic GABA using neurochemical imaging. The aim of this study was to investigate whether acute increases in synaptic GABA are detectable in the living human brain using the inverse agonist GABA-benzodiazepine receptor (GABA-BZR) positron emission tomography (PET) tracer, [(11)C]Ro15-4513. We examined the effect of 15 mg oral tiagabine, which increases synaptic GABA by inhibiting the GAT1 GABA uptake transporter, on [(11)C]Ro15-4513 binding in 12 male participants using a paired, double blind, placebo-controlled protocol. Spectral analysis was used to examine synaptic α1 and extrasynaptic α5 GABA-BZR subtype availability in brain regions with high levels of [(11)C]Ro15-4513 binding. We also examined the test-retest reliability of α1 and a5-specific [(11)C]Ro15-4513 binding in a separate cohort of 4 participants using the same spectral analysis protocol. Tiagabine administration produced significant reductions in hippocampal, parahippocampal, amygdala and anterior cingulate synaptic α1 [(11)C]Ro15-4513 binding, and a trend significance reduction in the nucleus accumbens. These reductions were greater than test-retest reliability, indicating that they are not the result of chance observations. Our results suggest that acute increases in endogenous synaptic GABA are detectable in the living human brain using [(11)C]Ro15-4513 PET. These findings have potentially major implications for the investigation of GABA function in brain disorders and in the development of new treatments targeting this neurotransmitter system., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
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