24 results on '"Dagher, Alain"'
Search Results
2. Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study
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Soliman, Alexandra, O'Driscoll, Gillian A, Pruessner, Jens, Holahan, Anne-Lise V, Boileau, Isabelle, Gagnon, Danny, and Dagher, Alain
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- 2008
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3. Differential Associations between Cortical Thickness and Striatal Dopamine in Treatment-Naïve Adults with ADHD vs. Healthy Controls.
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Cherkasova, Mariya V., Faridi, Nazlie, Casey, Kevin F., Larcher, Kevin, O'Driscoll, Gillian A., Hechtman, Lily, Joober, Ridha, Baker, Glen B., Palmer, Jennifer, Evans, Alan C., Dagher, Alain, Benkelfat, Chawki, and Leyton, Marco
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BRAIN physiology ,CEREBRAL cortex ,ATTENTION-deficit disorder in adults ,DOPAMINE ,POSITRON emission tomography ,PSYCHIATRIC diagnosis ,ATTENTION-deficit hyperactivity disorder ,THERAPEUTICS - Abstract
Alterations in catecholamine signaling and cortical morphology have both been implicated in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). However, possible links between the two remain unstudied. Here, we report exploratory analyses of cortical thickness and its relation to striatal dopamine transmission in treatment-naïve adults with ADHD and matched healthy controls. All participants had one magnetic resonance imaging (MRI) and two [
11 C]raclopride positron emission tomography scans. Associations between frontal cortical thickness and the magnitude of d-amphetamine-induced [11 C]raclopride binding changes were observed that were divergent in the two groups. In the healthy controls, a thicker cortex was associated with less dopamine release; in the ADHD participants the converse was seen. The same divergence was seen for baseline D2/3 receptor availability. In healthy volunteers, lower D2/3 receptor availability was associated with a thicker cortex, while in the ADHD group lower baseline D2/3 receptor availability was associated with a thinner cortex. Individual differences in cortical thickness in these regions correlated with ADHD symptom severity. Together, these findings add to the evidence of associations between dopamine transmission and cortical morphology, and suggest that these relationships are altered in treatment-naïve adults with ADHD. [ABSTRACT FROM AUTHOR]- Published
- 2017
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4. Is there a relation between novelty seeking, striatal dopamine release and frontal cortical thickness?
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Jaworska, Natalia, Cox, Sylvia M., Casey, Kevin F., Boileau, Isabelle, Cherkasova, Mariya, Larcher, Kevin, Dagher, Alain, Benkelfat, Chawki, and Leyton, Marco
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BRAIN abnormalities ,BRAIN imaging ,IMPULSIVE personality ,DOPAMINE ,DRUG delivery systems ,THERAPEUTICS - Abstract
Background: Novelty-seeking (NS) and impulsive personality traits have been proposed to reflect an interplay between fronto-cortical and limbic systems, including the limbic striatum (LS). Although neuroimaging studies have provided some evidence for this, most are comprised of small samples and many report surprisingly large effects given the challenges of trying to relate a snapshot of brain function or structure to an entity as complex as personality. The current work tested a priori hypotheses about associations between striatal dopamine (DA) release, cortical thickness (CT), and NS in a large sample of healthy adults. Methods: Fifty-two healthy adults (45M/7F; age: 23.8±4.93) underwent two positron emission tomography scans with [
11 C]raclopride (specific for striatal DA D2/3 receptors) with or without amphetamine (0.3 mg/kg, p.o.). Structural magnetic resonance image scans were acquired, as were Tridimensional Personality Questionnaire data. Amphetamine-induced changes in [11 C]raclopride binding potential values (ΔBPND ) were examined in the limbic, sensorimotor (SMS) and associative (AST) striatum. CT measures, adjusted for whole brain volume, were extracted from the dorsolateral sensorimotor and ventromedial/limbic cortices. Results: BPND values were lower in the amphetamine vs. no-drug sessions, with the largest effect in the LS. When comparing low vs. high LS ΔBPND groups (median split), higher NS2 (impulsiveness) scores were found in the high ΔBPND group. Partial correlations (age and gender as covariates) yielded a negative relation between ASTS ΔBPND and sensorimotor CT; trends for inverse associations existed between ΔBPND values in other striatal regions and frontal CT. In other words, the greater the amphetamine-induced striatal DA response, the thinner the frontal cortex. Conclusions: These data expand upon previously reported associations between striatal DA release in the LS and both NS related impulsiveness and CT in the largest sample reported to date. The findings add to the plausibility of these associations while suggesting that the effects are likely weaker than has been previously proposed. [ABSTRACT FROM AUTHOR]- Published
- 2017
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5. Cocaine cue--induced dopamine release in the human prefrontal cortex.
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Milella, Michele S., Fotros, Aryandokht, Gravel, Paul, Casey, Kevin F., Larcher, Kevin, Verhaeghe, Jeroen A. J., Cox, Sylvia M. L., Reader, Andrew J., Dagher, Alain, Benkelfat, Chawki, and Leyton, Marco
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DOPAMINE analysis ,BASAL ganglia ,BRAIN stem ,CELL receptors ,CELLS ,COCAINE ,DEOXY sugars ,DESIRE ,DRUG addiction ,FRONTAL lobe ,LIMBIC system ,RADIOPHARMACEUTICALS ,SELF-evaluation ,POSITRON emission tomography ,SAMPLE size (Statistics) - Abstract
Background: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. Methods: We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. Results: Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving. Limitations: Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release. Conclusion: In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms. [ABSTRACT FROM AUTHOR]
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- 2016
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6. Differential Striatal Dopamine Responses Following Oral Alcohol in Individuals at Varying Risk for Dependence.
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Setiawan, Elaine, Pihl, Robert O., Dagher, Alain, Schlagintweit, Hera, Casey, Kevin F., Benkelfat, Chawki, and Leyton, Marco
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ALCOHOLISM risk factors ,ANALYSIS of variance ,STATISTICAL correlation ,DOPAMINE ,ALCOHOL drinking ,FISHER exact test ,INTERVIEWING ,MAGNETIC resonance imaging ,RESEARCH methodology ,RESEARCH funding ,STATISTICS ,T-test (Statistics) ,POSITRON emission tomography ,DATA analysis ,RANDOMIZED controlled trials ,VISUAL analog scale ,REPEATED measures design ,DESCRIPTIVE statistics - Abstract
Background The neurobiology of risk for alcohol use disorders ( AUDs) remains poorly understood. Individual differences in vulnerability, though, have been indicated by subjective responses to alcohol ingestion and personality traits. Methods To investigate the relationship between these features and striatal dopamine (DA) responses to alcohol, we studied 26 healthy young social drinkers (21.3 ± 3.0 years old; 10.7 ± 8.8 drinks/wk) at varying risk for alcoholism. Each participant received 2 positron emission tomography [
11 C]raclopride scans after administration of either placebo or oral alcohol (1 ml/kg body weight of 94% alcohol, 0.75 g/kg) in a randomized and counterbalanced design. Results Subjects with high-risk subjective responses to alcohol had more family members with AUDs, greater alcohol use problems, and, in response to the alcohol challenge, significant decreases in [11 C]raclopride binding indicative of increased extracellular DA. In contrast, low-risk subjects exhibited increases in [11 C]raclopride binding in response to alcohol. The results were similar when risk groups were based on personality traits, although statistically less robust. Conclusions Changes in striatal DA in response to alcohol ingestion may be a neurobiological marker of vulnerability to AUDs. [ABSTRACT FROM AUTHOR]- Published
- 2014
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7. Individual Differences in Frontal Cortical Thickness Correlate with the d-Amphetamine-Induced Striatal Dopamine Response in Humans.
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Casey, Kevin F., Cherkasova, Mariya V., Larcher, Kevin, Evans, Alan C., Baker, Glen B., Dagher, Alain, Benkelfat, Chawki, and Leyton, Marco
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DOPAMINE ,LABORATORY animals ,PREFRONTAL cortex ,POSITRON emission tomography ,AMPHETAMINES ,PLACEBOS ,THERAPEUTICS - Abstract
The meso-striatal dopamine system influences responses to rewards and the motivation to seek them out. Marked individual differences in these responses are seen in laboratory animals, related in part to input from the prefrontal cortex. Here we measured the relation between cortical morphology and drug-induced striatal dopamine release in healthy young people. Participants were 24 (17 male, 7 female; age 23.0±6.2 years) stimulant drug-naive subjects who underwent PET [
11 C]raclopride scans with 0.3 mg/kg d-amphetamine orally and placebo, and an anatomical MRI scan for measuring cortical thickness. As expected, d-amphetamine produced significant reductions in [ 11C]raclopride binding potential in the striatum as a percentage of the value in the placebo condition. There was substantial individual variability in this response, which was correlated with cortical thickness in the frontal lobe as a whole. The association was strongest in the anterior part of the right lateral prefrontal cortex and bilateral supplementary motor area. At hicker cortex was correlated with a smaller dopamine response. Together, this work demonstrates inhumansan association between cortical thickness and the striatal dopamine response to drugs of abuse. Although prefrontal regulation of striatal function has been well studied, it was unclear whether the thickness of the prefrontal cortex was an acceptable proxy to the function of that region. These results suggest it is. [ABSTRACT FROM AUTHOR]- Published
- 2013
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8. Cocaine Cue-Induced Dopamine Release in Amygdala and Hippocampus: A High-Resolution PET [18F]Fallypride Study in Cocaine Dependent Participants.
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Fotros, Aryandokht, Casey, Kevin F, Larcher, Kevin, Verhaeghe, Jeroen AJ, Cox, Sylvia ML, Gravel, Paul, Reader, Andrew J, Dagher, Alain, Benkelfat, Chawki, and Leyton, Marco
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COCAINE ,DOPAMINE ,AMYGDALOID body ,HIPPOCAMPUS (Brain) ,POSITRON emission tomography ,SENSORIMOTOR cortex - Abstract
Drug-related cues are potent triggers for relapse in people with cocaine dependence. Dopamine (DA) release within a limbic network of striatum, amygdala and hippocampus has been implicated in animal studies, but in humans it has only been possible to measure effects in the striatum. The objective here was to measure drug cue-induced DA release in the amygdala and hippocampus using high-resolution PET with [
18 F]fallypride. Twelve cocaine-dependent volunteers (mean age: 39.6±8.0 years; years of cocaine use: 15.9±7.4) underwent two [18 F]fallypride high-resolution research tomography-PET scans, one with exposure to neutral cues and one with cocaine cues. [18 F]Fallypride non-displaceable-binding potential (BPND ) values were derived for five regions of interest (ROI; amygdala, hippocampus, ventral limbic striatum, associative striatum, and sensorimotor striatum). Subjective responses to the cues were measured with visual analog scales and grouped using principal component analysis. Drug cue exposure significantly decreased BPND values in all five ROI in subjects who had a high-, but not low-, craving response (limbic striatum: p=0.019, associative striatum: p=0.008, sensorimotor striatum: p=0.004, amygdala: p=0.040, and right hippocampus: p=0.025). Individual differences in the cue-induced craving response predicted the magnitude of [18 F]fallypride responses within the striatum (ventral limbic: r=0.581, p=0.048; associative: r=0.589, p=0.044; sensorimotor: r=0.675, p=0.016). To our knowledge this study provides the first evidence of drug cue-induced DA release in the amygdala and hippocampus in humans. The preferential induction of DA release among high-craving responders suggests that these aspects of the limbic reward network might contribute to drug-seeking behavior. [ABSTRACT FROM AUTHOR]- Published
- 2013
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9. Effects of lowered serotonin transmission on cocaine-induced striatal dopamine response: PET [¹¹C]raclopride study in humans.
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Cox, Sylvia M. L., Benkelfat, Chawki, Dagher, Alain, Delaney, J. Scott, Durand, France, Kolivakis, Theodore, Casey, Kevin F., and Leyton, Marco
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TRYPTOPHAN ,SEROTONIN ,COCAINE ,COMORBIDITY ,DOPAMINE ,DOPAMINERGIC mechanisms ,SUBSTANCE abuse & psychology ,TRYPTOPHAN metabolism ,INTRANASAL medication ,ANALYSIS of variance ,BASAL ganglia ,BENZAMIDE ,COMPARATIVE studies ,MAGNETIC resonance imaging ,RESEARCH methodology ,DOPAMINE uptake inhibitors ,MEDICAL cooperation ,RADIOPHARMACEUTICALS ,RESEARCH ,RESEARCH funding ,SUBSTANCE abuse ,POSITRON emission tomography ,EVALUATION research ,PHARMACODYNAMICS - Abstract
Background: Low serotonin transmission is thought to increase susceptibility to a wide range of substance use disorders and impulsive traits.Aims: To investigate the effects of lowered serotonin on cocaine-induced (1.0 mg/kg cocaine, self-administered intranasally) dopamine responses and drug craving.Method: In non-dependent cocaine users, serotonin transmission was reduced using the acute tryptophan depletion method. Striatal dopamine responses were measured using positron emission tomography with [(11)C]raclopride.Results: Acute 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.Conclusions: The 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. [ABSTRACT FROM AUTHOR]- Published
- 2011
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10. Anatomically distinct dopamine release during anticipation and experience of peak emotion to music.
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Salimpoor, Valorie N., Benovoy, Mitchel, Larcher, Kevin, Dagher, Alain, and Zatorre, Robert J.
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MUSIC psychology ,DOPAMINE ,ELATION ,POSITRON emission tomography ,CORPUS striatum ,PSYCHOPHYSIOLOGY ,MAGNETIC resonance imaging ,DOPAMINERGIC neurons - Abstract
Music, an abstract stimulus, can arouse feelings of euphoria and craving, similar to tangible rewards that involve the striatal dopaminergic system. Using the neurochemical specificity of [
11 C]raclopride positron emission tomography scanning, combined with psychophysiological measures of autonomic nervous system activity, we found endogenous dopamine release in the striatum at peak emotional arousal during music listening. To examine the time course of dopamine release, we used functional magnetic resonance imaging with the same stimuli and listeners, and found a functional dissociation: the caudate was more involved during the anticipation and the nucleus accumbens was more involved during the experience of peak emotional responses to music. These results indicate that intense pleasure in response to music can lead to dopamine release in the striatal system. Notably, the anticipation of an abstract reward can result in dopamine release in an anatomical pathway distinct from that associated with the peak pleasure itself. Our results help to explain why music is of such high value across all human societies. [ABSTRACT FROM AUTHOR]- Published
- 2011
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11. Motion correction of multi-frame PET data in neuroreceptor mapping: Simulation based validation
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Costes, Nicolas, Dagher, Alain, Larcher, Kevin, Evans, Alan C., Collins, D. Louis, and Reilhac, Anthonin
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NEURAL receptors , *BRAIN mapping , *POSITRON emission tomography , *VOXEL-based morphometry , *IMAGE registration , *SIMULATION methods & models , *DIAGNOSTIC imaging research - Abstract
Abstract: Patient motion during positron emission tomography scanning can affect the accuracy of the data analysis in two ways: 1) movement occurring during emission data acquisition alters the time activity curves (TACs), measured at a voxel or region of interest (ROI), and hence introduces errors in the parameter estimates derived from kinetic modeling; 2) emission–transmission mismatches introduce errors during attenuation and scatter correction, and hence in the radioactivity distribution estimates for each time frame of the scan. With the aim of designing an algorithm-based frame realignment method, we first conducted investigations that aimed at optimizing the parameters of a coregistration method, such as the choice of the target volume and the similarity criterion. Based on these results we designed a novel frame realignment strategy in a multi-step algorithm using uncorrected reconstructed images, cross-correlation similarity criteria for the determination of inter-frame motion parameters and emission-transmission mismatch for each frame. Features and validation results are reported here based on a multi-subject simulated [11C]raclopride dynamic PET scan database incorporating intra-frame movements of various magnitudes and with various times of occurrence. Performances of the proposed algorithm were evaluated at regional and voxel-based level for binding potential parametric images. [Copyright &y& Elsevier]
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- 2009
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12. Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study.
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Soliman, Alexandra, O'Driscoll, Gillian A., Pruessner, Jens, Holahan, Anne-Lise V., Boileau, Isabelle, Gagnon, Danny, and Dagher, Alain
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PSYCHOLOGICAL stress ,DOPAMINE ,BIOGENIC amines ,PSYCHOSES ,DRUGS ,POSITRON emission tomography - Abstract
Drugs that increase dopamine levels in the brain can cause psychotic symptoms in healthy individuals and worsen them in schizophrenic patients. Psychological stress also increases dopamine release and is thought to play a role in susceptibility to psychotic illness. We hypothesized that healthy individuals at elevated risk of developing psychosis would show greater striatal dopamine release than controls in response to stress. Using positron emission tomography and [
11 C]raclopride, we measured changes in synaptic dopamine concentrations in 10 controls and 16 psychometric schizotypes; 9 with perceptual aberrations (PerAb, ie positive schizotypy) and 7 with physical anhedonia (PhysAn, ie negative schizotypy). [11 C]Raclopride binding potential was measured during a psychological stress task and a sensory-motor control. All three groups showed significant increases in self-reported stress and cortisol levels between the stress and control conditions. However, only the PhysAn group showed significant stress-induced dopamine release. Dopamine release in the entire sample was significantly negatively correlated with smooth pursuit gain, an endophenotype linked to frontal lobe function. Our findings suggest the presence of abnormalities in the dopamine response to stress in negative symptom schizotypy, and provide indirect evidence of a link to frontal function.Neuropsychopharmacology (2008) 33, 2033–2041; doi:10.1038/sj.npp.1301597; published online 24 October 2007 [ABSTRACT FROM AUTHOR]- Published
- 2008
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13. Fibromyalgia patients show an abnormal dopamine response to pain.
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Wood, Patrick B., Schweinhardt, Petra, Jaeger, Erik, Dagher, Alain, Hakyemez, Helene, Rabiner, Eugenii A., Bushnell, M. Catherine, and Chizh, Boris A.
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FIBROMYALGIA ,DOPAMINE ,PAIN management ,FASCIITIS ,NEURAL transmission ,EFFERENT pathways ,DOPAMINERGIC mechanisms ,CATECHOLAMINES - Abstract
Fibromyalgia is characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances. Accumulating evidence indicates that fibromyalgia may involve a dysfunction of modulatory systems in the brain. While brain dopamine is best known for its role in pleasure, motivation and motor control, recent evidence suggests that it is also involved in pain modulation. Because dopamine is implicated in both pain modulation and affective processing, we hypothesized that fibromyalgia may involve a disturbance of dopaminergic neurotransmission. Fibromyalgia patients and matched healthy control subjects were subjected to deep muscle pain produced by injection of hypertonic saline into the anterior tibialis muscle. In order to determine the endogenous release of dopamine in response to painful stimulation, we used positron emission tomography to examine binding of [
11 C]-raclopride (D2/D3 ligand) in the brain during injection of painful hypertonic saline and nonpainful normal saline. Fibromyalgia patients experienced the hypertonic saline as more painful than healthy control subjects. Control subjects released dopamine in the basal ganglia during the painful stimulation, whereas fibromyalgia patients did not. In control subjects, the amount of dopamine release correlated with the amount of perceived pain but in fibromyalgia patients no such correlation was observed. These findings provide the first direct evidence that fibromyalgia patients have an abnormal dopamine response to pain. The disrupted dopaminergic reactivity in fibromyalgia patients could be a critical factor underlying the widespread pain and discomfort in fibromyalgia and suggests that the therapeutic effects of dopaminergic treatments for this intractable disorder should be explored. [ABSTRACT FROM AUTHOR]- Published
- 2007
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14. Conditioned Dopamine Release in Humans: A Positron Emission Tomography [11C]Raclopride Study with Amphetamine.
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Boileau, Isabelle, Dagher, Alain, Leyton, Marco, Welfeld, Krzysztof, Booij, Linda, Diksic, Mirko, and Benkelfat, Chawki
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DRUG abuse , *DOPAMINE , *DRUGS of abuse , *POSITRON emission tomography , *AMPHETAMINE abuse , *PLACEBOS - Abstract
Studies in laboratory rodents suggest that previously neutral stimuli repeatedly paired with the administration of drugs of abuse can acquire the ability to increase striatal dopamine release. This conditioned neurochemical response is believed to prompt drug seeking in animals and has been hypothesized to contribute to drug craving and relapse in substance abusers. In the present study, we used positron emission tomography and [11C]raclopride to investigate whether amphetamine-predictive stimuli can elicit striatal dopamine release in humans. Nine healthy male volunteers received a capsule containing amphetamine tablets (0.3 mg/kg) on three separate occasions approximately every other day (mean ± SD, 2.25 ± 1.13 d apart) in the same environment (scanner suite). At least 2 weeks later, the amphetamine was switched to a placebo of identical appearance and given in the same environmental context. [11C]Raclopride binding to dopamine D2/3 receptors was assessed after exposure to the first amphetamine-containing pill, after placebo administration, and during a control (no pill) scan. Relative to the control scan, amphetamine administration decreased [11C]raclopride binding potential by 22% in the ventral striatum and 11% in the putamen. Placebo also decreased [11C]raclopride binding potential in the ventral striatum and did so with the same amplitude as amphetamine (23%). These results suggest that cues associated with amphetamine increase dopamine transmission, providing evidence that this system is involved in reward prediction in humans. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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15. Dopamine Transmission in the Human Striatum during Monetary Reward Tasks.
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Zald, David H., Boileau, Isabelle, El-Dearedy, Wael, Gunn, Roger, McGlone, Francis, Dichter, Gabriel S., and Dagher, Alain
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DOPAMINE ,POSITRON emission tomography ,BEHAVIOR ,CAUDATE nucleus ,NUCLEUS accumbens - Abstract
Previous studies have demonstrated the ability of the [
11 C]raclopride positron emission tomography (PET) technique to measure behaviorally induced changes in endogenous dopamine transmission in humans. However, these studies have lacked well matched sensorimotor control conditions, making it difficult to know what sensory, cognitive, or motor features contributed to changes in dopaminergic activity. Here we report on [11 C]raclopride PET studies in which healthy humans performed card selection tasks for monetary rewards. During separate scans, subjects completed a variable ratio (VR) reward schedule with a 25% reward rate in which they did not know the outcome of their responses in advance, a fixed ratio (FR) 25% reward schedule in which outcomes were fully predictable, and a sensorimotor control (SC) condition involving similar sensory and motor demands but no rewards. Relative to the SC condition, the FR schedule produced only modest increases in dopamine transmission and no decreases relative to the SC condition. In contrast, the VR schedule produced significant increases in dopamine transmission in the left medial caudate nucleus while simultaneously producing significant decreases in other areas of the caudate and putamen. These data indicate: (1) the feasibility of measuring alterations in dopamine transmission even after controlling for sensorimotor features and (2) the complex and regionally specific influence of VR schedules on dopamine transmission. The implications of these results are discussed in relation to conflicting models of dopaminergic functioning arising from studies using electrophysiological and microdialysis techniques in animals. [ABSTRACT FROM AUTHOR]- Published
- 2004
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16. Dopamine Release in Response to a Psychological Stress in Humans and Its Relationship to Early Life Maternal Care: A Positron Emission Tomography Study Using [11C]Raclopride.
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Dagher, Alain, Pruessner, Jens C., Champagne, Frances, and Meaney, Michael J.
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DOPAMINE , *PSYCHOLOGICAL stress , *HYPOTHALAMIC-pituitary-adrenal axis , *NEUROENDOCRINOLOGY , *POSITRON emission tomography - Abstract
Mesolimbic dopamine is thought to play a role in the processing of rewards. However, animal studies also demonstrate dopamine release in response to aversive stressful stimuli. Also, in animal studies, disruptions of the mother-infant relationship have been shown to have long-lasting effects on the mesolimbic dopamine system and the hypothalamic-pituitary adrenal axis. We therefore investigated dopamine release in response to stress in human subjects, considering the relationship to early life parental care. We screened 120 healthy young college students for parental care in early life using a combination of telephone interviews and questionnaires. Five students from the top end and five students from the bottom end of the parental care distribution were then invited for a positron emission tomography study using [11C]raclopride and a psychosocial stress task. The psychosocial stressor caused a significant release of dopamine in the ventral striatum as indicated by a reduction in [11C]raclopride binding potential in the stress versus resting condition in subjects reporting low parental care. Moreover, the magnitude of the salivary cortisol response to stress was significantly correlated with the reduction in [11C C]raclopride binding in the ventral striatum (r = 0.78), consistent with a facilitating effect of cortisol on dopamine neuron firing. These data suggest that aversive stressful events can be associated with mesolimbic dopamine release in humans, and that the method presented here may be useful to study the effects of early life events on neurobiological stress systems. [ABSTRACT FROM AUTHOR]
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- 2004
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17. Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men.
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Leyton, Marco, Dagher, Alain, Boileau, Isabelle, Casey, Kevin, Baker, Glenn B., Diksic, Mirko, Gunn, Roger, Young, Simon N., and Benkelfat, Chawki
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DOPAMINE , *AMPHETAMINES , *PHENYLALANINE , *TYROSINE , *POSITRON emission tomography , *CATECHOLAMINES - Abstract
Acute phenylalanine/tyrosine depletion (APTD) has been proposed as a new method to decrease catecholamine neurotransmission safely, rapidly, and transiently. Validation studies in animals are encouraging, but direct evidence in human brain is lacking. In the present study, we tested the hypothesis that APTD would reduce stimulated dopamine (DA) release, as assessed by positron emission tomography (PET) and changes in [11C]raclopride binding potential (BP), a measure of DA D2/D3 receptor availability. Eight healthy men received two PET scans, both following d-amphetamine, 0.3 mg/kg, p.o., an oral dose known to decrease [11C]raclopride BP in ventral striatum. On the morning before each scan, subjects ingested, in counter-balanced order, an amino-acid mixture deficient in the catecholamine precursors, phenylalanine, and tyrosine, or a nutritionally balanced mixture. Brain parametric images were generated by calculating [11C]raclopride BP at each voxel. BP values were extracted from the t-map (threshold: t=4.2, equivalent to p<0.05, Bonferroni corrected) and a priori identified regions of interest from each individual's coregistered magnetic resonance images. Both receptor parametric mapping and region of interest analyses indicated that [11C]raclopride binding was significantly different on the two test days in the ventral striatum (peak t=6.31; x=-25, y=-8, and z=0.1). In the t-map defined cluster, [11C]raclopride BP values were 11.8 ± 11.9% higher during the APTD session (p<0.05). The reduction in d-amphetamine-induced DA release exhibited a linear association with the reduction in plasma tyrosine levels (r = -0.82, p < 0.05). Together, the results provide the first direct evidence that APTD decreases stimulated DA release in human brain. APTD may be a suitable new tool for human neuropsychopharmacology research. [ABSTRACT FROM AUTHOR]
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- 2004
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18. Mapping dopamine with positron emission tomography: A note of caution.
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Dagher, Alain and Palomero-Gallagher, Nicola
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POSITRON emission tomography , *DOPAMINE - Published
- 2020
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19. Striatal Dopamine Responses to Intranasal Cocaine Self-Administration in Humans
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Cox, Sylvia M.L., Benkelfat, Chawki, Dagher, Alain, Delaney, J. Scott, Durand, France, McKenzie, Samuel A., Kolivakis, Theodore, Casey, Kevin F., and Leyton, Marco
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DOPAMINE receptors , *COCAINE abuse , *POSITRON emission tomography , *PLACEBOS , *CHEMICAL inhibitors , *DOPAMINERGIC mechanisms , *CORPUS striatum - Abstract
Background: The effect of self-administered cocaine on extracellular dopamine (DA) levels has not been measured in humans. Methods: Ten nondependent cocaine users underwent positron emission tomography [11C]raclopride scans following intranasal self-administration of cocaine hydrochloride (1.0 mg/kg) and placebo powder. Results: Compared with placebo, intranasal cocaine self-administration decreased [11C]raclopride binding values in the ventral limbic striatum and putamen. Individual differences in the magnitude of the [11C]raclopride response in the ventral striatum were predicted by lifetime histories of stimulant drug use. Conclusions: The results suggest that 1) intranasal cocaine self-administration increases synaptic DA levels in human striatum and 2) prior use of stimulant drugs on the street is associated with progressively greater cocaine-induced DA responses. These dopaminergic effects might influence susceptibility to drug–seeking behavior and the progression to substance abuse. [Copyright &y& Elsevier]
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- 2009
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20. Normal cognition in Parkinson's disease may involve hippocampal cholinergic compensation: An exploratory PET imaging study with [18F]-FEOBV.
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Legault-Denis, Camille, Aghourian, Meghmik, Soucy, Jean-Paul, Rosa-Neto, Pedro, Dagher, Alain, Aumont, Etienne, Wickens, Rebekah, and Bedard, Marc-André
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POSITRON emission tomography , *PARKINSON'S disease , *COGNITION , *HIPPOCAMPAL innervation , *MILD cognitive impairment - Abstract
Background: Severe cholinergic degeneration is known to occur in Parkinson's disease (PD) and is thought to play a primary role in the cognitive decline associated with this disease. Although cholinergic losses occur in all patients with PD, cognitive performance remains normal for many of them, suggesting compensatory mechanisms in those.Objectives: This exploratory study aimed at verifying if normal cognition in PD may involve distinctive features of the brain cholinergic systems.Methods: Following extensive neuropsychological screening in 25 patients with PD, 12 were selected and evenly distributed between a cognitively normal (PD-CN) group, and a mild cognitive impairment (PD-MCI) group. Each group was compared with matched healthy volunteers (HV) on standardized cognitive scales (MoCA, PDCRS), and PET imaging with [18F]-FEOBV, a sensitive measurement of brain cholinergic innervation density.Results: [18F]-FEOBV uptake reductions were observed in PD-CN as well as in PD-MCI, with the lowest values located in the posterior cortical areas. However, in PD-CN but not in PD-MCI, there was a significant and bilateral increase of [18F]-FEOBV uptake, exclusively located in the hippocampus. Significant correlations were observed between cognitive performance and hippocampal [18F]-FEOBV uptake.Conclusion: These findings suggest a compensatory upregulation of the hippocampal cholinergic innervation in PD-CN, which might underly normal cognitive performances in spite of cortical cholinergic denervation in other regions. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
21. Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers
- Author
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Small, Dana M., Jones-Gotman, Marilyn, and Dagher, Alain
- Subjects
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DOPAMINE , *POSITRON emission tomography , *BRAIN - Abstract
Seven healthy subjects underwent two [11C]raclopride positron emission tomography (PET) scans, one following a 16-h fast and the other after consumption of a favorite meal (following a 16-h fast) in counterbalanced fashion. Before and after each scan subjects gave ratings of hunger/fullness and desire to eat. In addition, meal pleasantness ratings were collected immediately after consumption of the favorite meal. PET data were analyzed using brain parametric maps to generate regions of statistically significant change, as well as regions of interest manually drawn on each individual''s coregistered anatomical image. [11C]Raclopride binding potential was compared across the two states (hungry and full). A significant reduction in binding potential was observed in the full compared to the hungry state in the dorsal putamen and caudate nucleus, indicative of dopamine release. There were no changes elsewhere in the striatum. A correlation was observed between the reduction in [11C]raclopride binding and meal pleasantness ratings, but not with desire to eat (hunger) or satiety after eating. These results suggest that feeding is associated with dopamine release in the dorsal, but not the ventral striatum, and that the amount of dopamine released correlates with the degree of experienced pleasure. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
- View/download PDF
22. Striatal D1 and D2 signaling differentially predict learning from positive and negative outcomes.
- Author
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Cox, Sylvia M.L., Frank, Michael J., Larcher, Kevin, Fellows, Lesley K., Clark, Crystal A., Leyton, Marco, and Dagher, Alain
- Subjects
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DOPAMINE receptors , *NEUROTRANSMITTERS , *DOPAMINERGIC neurons , *CELLULAR signal transduction , *HEALTH outcome assessment , *POSITRON emission tomography , *BRAIN imaging - Abstract
The extent to which we learn from positive and negative outcomes of decisions is modulated by the neurotransmitter dopamine. Dopamine neurons burst fire in response to unexpected rewards and pause following negative outcomes. This dual signaling mechanism is hypothesized to drive both approach and avoidance behavior. Here we test a prediction deriving from a computational reinforcement learning model, in which approach is mediated via activation of the direct cortico-striatal pathway due to striatal D1 receptor stimulation, while avoidance occurs via disinhibition of indirect pathway striatal neurons secondary to a reduction of D2 receptor stimulation. Using positron emission tomography with two separate radioligands, we demonstrate that individual differences in human approach and avoidance learning are predicted by variability in striatal D1 and D2 receptor binding, respectively. Moreover, transient dopamine precursor depletion improved learning from negative outcomes. These findings support a bidirectional modulatory role for striatal dopamine in reward and avoidance learning via segregated D1 and D2 cortico-striatal pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
23. Dopamine modulates default mode network deactivation in elderly individuals during the Tower of London task
- Author
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Nagano-Saito, Atsuko, Liu, Jiaqiang, Doyon, Julien, and Dagher, Alain
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NEUROPSYCHOLOGY research , *PARKINSON'S disease patients , *DOPAMINE , *PREFRONTAL cortex , *BIOLOGICAL neural networks , *APOMORPHINE , *POSITRON emission tomography - Abstract
Abstract: Task-induced deactivation is frequently reported in the ventro-medial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), regions considered to belong to the default mode network. To investigate the effect of dopamine on task-induced deactivation, we used positron emission tomography to measure cerebral blood flow during performance of the Tower of London task before and after administration of the dopamine receptor agonist apomorphine in six healthy volunteers (49–66 years old) and six Parkinson disease patients (52–69 years old). Although task-induced deactivation was observed in the vmPFC and PCC in both groups and in both conditions, an inverse correlation between activation and problem complexity was observed in the vmPFC only in the apomorphine condition. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
24. Deactivation of the Limbic System During Acute Psychosocial Stress: Evidence from Positron Emission Tomography and Functional Magnetic Resonance Imaging Studies
- Author
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Pruessner, Jens C., Dedovic, Katarina, Khalili-Mahani, Najmeh, Engert, Veronika, Pruessner, Marita, Buss, Claudia, Renwick, Robert, Dagher, Alain, Meaney, Michael J., and Lupien, Sonia
- Subjects
- *
BRAIN imaging , *POSITRON emission tomography , *BRAIN diseases ,DIAGNOSIS of brain abnormalities - Abstract
Background: Stress-induced metabolic changes can have detrimental health effects. Newly developed paradigms to investigate stress in neuroimaging environments allow the assessment of brain activation changes in association with the perception of and the metabolic response to stress. Methods: We exposed human subjects to a psychosocial stressor in one positron emission tomography (n = 10) and one functional magnetic resonance imaging (fMRI; n = 40) experiment. Results: We observed a profound deactivation of limbic system components including hippocampus, hypothalamus, medio-orbitofrontal cortex and anterior cingulate cortex in subjects who reacted to the stressor with a significant increase of the endocrine stress marker cortisol. Further, in the fMRI study, the degree of deactivation in the hippocampus was correlated with the release of cortisol in response to the stress task. Conclusions: The observed deactivation of limbic system structures suggests elevated activation at rest and during nonstressful situations. A model is proposed where the observed reduction in limbic system activity is essential for the initiation of the stress response. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
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