ADHD: increased dopamine receptor availability linked to attention deficit and low neonatal cerebral blood flow

Lou, Hans C.; Rosa, Pedro; Pryds, Ole; Karrebaek, Hanne; Lunding, Jytte Merete Carlsen; Cumming, Paul; Gjedde, Albert

doi:10.1111/j.1469-8749.2004.tb00469.x

Cited by 67 publications

(22 citation statements)

References 27 publications

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“…More recently, growing evidence has raised the possibility of striatal dysfunction associated with ADHD and autism (Durston et al 2003;Lou et al 2004;Di Martino et al 2011;Peca et al 2011). Interestingly, a notable number of mouse models for neuropsychiatric disorders share a common phenotype of elevated locomotor activity (Bolivar et al 2004;Welch et al 2007;Dzirasa et al 2010;Penagarikano et al 2011;Won et al 2012).…”

Section: The Modulation Of Excitatory and Inhibitory Balance In Locommentioning

confidence: 99%

Functional roles of neurotransmitters and neuromodulators in the dorsal striatum

Kim

Bakes

et al. 2012

Learn. Mem.

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The dorsal striatum, with its functional microcircuits galore, serves as the primary gateway of the basal ganglia and is known to play a key role in implicit learning. Initially, excitatory inputs from the cortex and thalamus arrive on the direct and indirect pathways, where the precise flow of information is then regulated by local GABAergic interneurons. The balance of excitatory and inhibitory transmission in the dorsal striatum is modulated by neuromodulators such as dopamine and acetylcholine. Under pathophysiological states in the dorsal striatum, an alteration in excitatory and inhibitory transmission may underlie dysfunctional motor control. Here, we review the cellular connections and modulation of striatal microcircuits and propose that modulating the excitatory and inhibitory balance in synaptic transmission of the dorsal striatum is important for regulating locomotion.The dorsal striatum is best known for its role in decision-making, especially in action selection and initiation through the convergence of sensorimotor, cognitive, and motivational information (DeLong 1990;Smith et al. 1998;Balleine et al. 2007). As the primary input of the basal ganglia, the striatum receives glutamatergic inputs from the cortex and thalamus and in turn projects GABAergic outputs to the globus pallidus and substantia nigra pars reticulata (SNr). Inputs from the cortex and thalamus both form excitatory synaptic connections on medium spiny neurons (MSN) in which cortical afferents are from the sensory, motor, and associational cortex (Bolam et al. 2000), and thalamic afferents are from the intralaminar thalamic nuclei (Doig et al. 2010). These glutamatergic inputs are then processed in the dorsal striatum where numerous connections between various types of neurons exist. Thus, the complexity of neuronal circuits has made it difficult to elucidate the functional roles of the striatum. Recently, studies focused on interneurons that reside in the dorsal striatum have characterized the physiological features and functional connections. For example, parvalbumin-expressing fastspiking interneurons (PV-FSI) and neuropeptide-Y positive lowthreshold spiking interneurons (NPY-LTS) form synaptic connections with MSNs and regulate the firing activity of the principal neuron MSNs (Koos and Tepper 1999;Gittis et al. 2010;Chuhma et al. 2011). These interneurons were shown to have distinct firing patterns and connections, and thus they may exert different effects on MSNs. Other crucial connections are the cholinergic, dopaminergic, and serotonergic axons that strongly innervate the dorsal striatum. These projections are essential for modulating striatal circuits and disruption of such signaling can result in movement impairments and neurological disorders such as Huntington's disease (Lovinger 2010). This review summarizes recent reports of the microcircuits present in the dorsal striatum, although serotonergic signaling is excluded, and suggests a putative role for striatal microcircuits in motor dysfunction and/or hyperactivity that ...

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Section: The Modulation Of Excitatory and Inhibitory Balance In Locommentioning

confidence: 99%

Functional roles of neurotransmitters and neuromodulators in the dorsal striatum

Kim

Bakes

et al. 2012

Learn. Mem.

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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%

“…Executive functions rely on frontalstriatal circuitry (Alexander et al, 1990), and functional imaging studies have linked reduced activation in frontalstriatal circuitry in ADHD to performance deficits on executive function tasks (Dickstein et al, 2006). However, few studies to date have linked molecular imaging measures of striatal DA function to neurocognitive performance in ADHD (Lou et al, 2004;Rosa-Neto et al, 2005).…”

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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“…The dopamine system, particularly in the basal ganglia is highly susceptible to hypoxia and relations of ADHD behavior and hypoxia at birth have been reported (Lou et al, 2004). In addition, ADHD symptoms are seen after childhood stroke, particularly with lesions in the basal ganglia, especially the putamen (Max et al, 2002), and orbitofrontal and mesial prefrontal cortices (Max et al, 2005a), and traumatic brain injury affecting basal ganglia and orbitofrontal regions (Gerring et al, 2000;Herskovits et al, 1999;Max et al, 2005b).…”

Section: Introductionmentioning

confidence: 99%

A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: Evidence for genetic and environmental heterogeneity in the developing brain

et al. 2007

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Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the etiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes, we performed Voxel-Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high-risk for ADHD. Brain differences between concordant high-risk twin pairs and concordant low-risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low-risk and high-risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low-risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high-risk pairs showed volume loss in orbitofrontal subdivisions. High-risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high-risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed actionattentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) vs. environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD.

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ADHD: increased dopamine receptor availability linked to attention deficit and low neonatal cerebral blood flow

Cited by 67 publications

References 27 publications

Functional roles of neurotransmitters and neuromodulators in the dorsal striatum

Functional roles of neurotransmitters and neuromodulators in the dorsal striatum

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

A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: Evidence for genetic and environmental heterogeneity in the developing brain

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