Evaluating Dopamine Reward Pathway in ADHD

Volkow, Nora D.; Wang, Gene‐Jack; Kollins, Scott H.; Wigal, Tim; Newcorn, Jeffrey H.; Telang, Frank; Fowler, Joanna S.; Zhu, Wei; Logan, Jean; Ma, Yeming; Pradhan, Kith; Wong, Christopher; Swanson, James M.

doi:10.1001/jama.2009.1308

Cited by 572 publications

(456 citation statements)

References 55 publications

(54 reference statements)

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“…The training also includes delivery of rewards for correct performance, which likely acts on the basal ganglia, although both training and placebo groups would have received rewards. Stimulant treatment, such as methylphenidate, is known to act directly on brain regions associated with disrupted dopamine reward pathways in ADHD [62,63] and may be responsible for the global effects seen with stimulant treatment in ADHD. Understanding and comparing the effects of treatments that directly manipulate dopaminergic functioning via pharmacological approaches versus delivering of conditioned rewards as feedback within the training system have not been conducted.…”

Section: Discussionmentioning

confidence: 99%

Will Working Memory Training Generalize to Improve Off-Task Behavior in Children with Attention-Deficit/Hyperactivity Disorder?

et al. 2012

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Computerized working memory and executive function training programs designed to target specific impairments in executive functioning are becoming increasingly available, yet how well these programs generalize to improve functional deficits in disorders, such as attentiondeficit/hyperactivity disorder (ADHD), beyond the training context is not well-established. The aim of this study was to examine the extent to which working memory (WM) training in children with ADHD would diminish a core dysfunctional behavior associated with the disorder, "offtask" behavior during academic task performance. The effect of computerized WM training (adaptive) was compared to a placebo condition (nonadaptive) in a randomized, doubleblind, placebo-controlled design in 26 children (18 males; age, 7 to 14 years old) diagnosed with ADHD. Participants completed the training in approximately 25 sessions. The Restricted Academic Situations Task (RAST) observational system was used to assess aspects of off-task behavior during the completion of an academic task. Traditional measures of ADHD symptoms (Conners' Parent Rating Scale) and WM ability (standardized WM tests) were also collected. WM training led to significant reductions in off-task ADHDassociated behavior on the RAST system and improvement on WM tests. There were no significant differences between groups in improvement on parent rating scales. Findings lend insight into the generalizability of the effects of WM training and the relation between deficits in WM and off-task behavioral components of ADHD. These preliminary data suggest WM training may provide a mechanism for indirectly altering academic performance in children with ADHD.

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Section: Discussionmentioning

confidence: 99%

Will Working Memory Training Generalize to Improve Off-Task Behavior in Children with Attention-Deficit/Hyperactivity Disorder?

et al. 2012

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“…Human brain imaging and animal studies have strongly suggested that a hypofunctional dopamine system underlies the core symptoms of attention deficit/hyperactivity disorder (ADHD) [15][16][17][18] . The low-dopamine theory explains why low levels of stimulant drugs mildly increase brain dopamine levels but paradoxically reduce the hyperactivity in human ADHD.…”

Section: Selective Activation Of Midbrain Dopaminergic Neuronsmentioning

confidence: 99%

Pharmacogenetic activation of midbrain dopaminergic neurons induces hyperactivity

et al. 2013

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Dopaminergic neurons regulate and organize numerous important behavioral processes including motor activity. Consistently, manipulation of brain dopamine concentrations changes animal activity levels. Dopamine is synthesized by several neuronal populations in the brain. This study was carried out to directly test whether selective activation of dopamine neurons in the midbrain induces hyperactivity. A pharmacogenetic approach was used to activate midbrain dopamine neurons, and behavioral assays were conducted to determine the effects on mouse activity levels. Transgenic expression of the evolved hM3Dq receptor was achieved by infusing Creinducible AAV viral vectors into the midbrain of DATCre mice. Neurons were excited by injecting the hM3Dq ligand clozapine-N-oxide (CNO). Mouse locomotor activity was measured in an open field. The results showed that CNO selectively activated midbrain dopaminergic neurons and induced hyperactivity in a dose-dependent manner, supporting the idea that these neurons play an important role in regulating motor activity.

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“…For example, both increases and decreases have been reported for D 2 /D 3 receptor availability and for dopamine transporter (DAT) binding in ADHD patients vs controls (Lou et al, 2004;Spencer et al, 2005;Spencer et al, 2013;Volkow et al, 2007a;Volkow et al, 2009). Only one study has examined DA release in untreated ADHD (Volkow et al, 2007b).…”

Section: Introductionmentioning

confidence: 99%

Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

Cherkasova

Faridi

Casey

et al. 2013

Neuropsychopharmacol

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Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [ 11 C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87±8.65) and 18 healthy male controls (age: 25.44±6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [ 11 C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [ 11 C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.

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Evaluating Dopamine Reward Pathway in ADHD

Cited by 572 publications

References 55 publications

Will Working Memory Training Generalize to Improve Off-Task Behavior in Children with Attention-Deficit/Hyperactivity Disorder?

Will Working Memory Training Generalize to Improve Off-Task Behavior in Children with Attention-Deficit/Hyperactivity Disorder?

Pharmacogenetic activation of midbrain dopaminergic neurons induces hyperactivity

Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

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