Involvement of Norepinephrine in the Control of Activity and Attentive Processes in Animal Models of Attention Deficit Hyperactivity Disorder

Viggiano, D.; Ruocco, L; Arcieri, S.; Sadile, A.G.

doi:10.1155/np.2004.133

Cited by 62 publications

(37 citation statements)

References 117 publications

(133 reference statements)

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“…A reduction in the level of NE in the synapse appears to down regulate the level of NET [3]. Recent research has clearly demonstrated a close association between the changes in the distribution of NET in the human brain and various diseases including CNS disorders like depression [4] attention deficit hyperactivity disorder (ADHD) [5,6] and Alzheimer's disease [7]. Non-invasive imaging with highly selective radiolabeled probes would allow us to monitor and quantify the effect of treatment (drug occupancy) or the lack thereof on NET.…”

Section: Introductionmentioning

confidence: 99%

(R)-N-Methyl-3-(3-125I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

Balagopal¹,

Kung²,

Lieberman³

et al. 2008

Nuclear Medicine and Biology

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Alterations in the serotonin and norepinephrine neuronal functions have been observed in patients with major depression. Several antidepressants bind to both serotonin transporters (SERT) and norepinephrine transporters (NET). The ability to image NET in the human brain would be a useful step toward understanding how alterations in NET relate to disease. In this study, we report the synthesis and characterization of a new series of derivatives of iodo-nisoxetine (INXT), a known radioiodinated probe. The most promising, (R)-N-methyl-3-(3-iodopyridin-2-yloxy)-3-phenylpropylamine (PYINXT) 9, displayed a high and saturable binding to NET with a K d value of 0.53 ± 0.03 nM. Biodistribution studies of [ 125 I]PYINXT in rats showed moderate initial brain uptake (0.54 %dose/organ at 2 min) with a relatively fast washout from the brain (0.16 %dose/organ at 2 hr) as compared to [ 125 I]INXT, 7. The hypothalamus (a NET rich region) to striatum (a region devoid of NET) ratio was found to be 2.14 at 4 hr post i.v. injection. The preliminary results suggest that this improved iodinated ligand, when labeled with 123 I, may be useful for mapping NET binding sites with SPECT in the living human brain.

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Section: Introductionmentioning

confidence: 99%

(R)-N-Methyl-3-(3-125I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

Balagopal¹,

Kung²,

Lieberman³

et al. 2008

Nuclear Medicine and Biology

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“…DA has received prominent attention for its role in circuits supporting reward, attention, and movement, with perturbed DA signaling associated with addiction, attention-deficit hyperactivity disorder (ADHD), schizophrenia, and Parkinson's disease (Viggiano et al, 2004b;Segura-Aguilar et al, 2014;Howes et al, 2015;Nutt et al, 2015 ). NE plays a prominent role in arousal, attention, executive function, and stress responses (Harley, 2004;Viggiano et al, 2004a;Morilak et al, 2005), with disorders such as ADHD, posttraumatic stress disorder. and depression often linked to disrupted central nervous system NE signaling (Southwick et al, 1999;Kim et al, 2008;Goddard et al, 2010).…”

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confidence: 99%

Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters

Bermingham

Blakely

2016

Pharmacol Rev

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“…These processes may be mediated through activation of the norepinephrine α -2 and/or dopamine D 1 receptors [21][22][23]. Recently, it was shown that the atomoxetine and methylphenidate increase cortical histamine release in rats [19].Besides the well-documented role of dopamine and noradrenergic neurotransmission imbalance in the pathophysiology of ADHD and in the behavioural alterations of SHRs, several reports have proposed functional alterations in histamine neurotransmission in ADHD [19,24,25], making the effect of atomoxetine on histamine neurotransmission in SHR somewhat trivial. It is well known that brain histamine…”

mentioning

confidence: 99%

Atomoxetine Increases Histamine Release and Improves Learning Deficits in an Animal Model of Attention‐Deficit Hyperactivity Disorder: The Spontaneously Hypertensive Rat

Liu

Yang

Lei

et al. 2008

Basic Clin Pharma Tox

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Substantial development in the pharmacological treatment for attention-deficit hyperactivity disorder (ADHD) has been made recently including approval of new non-stimulant agents targeting noradrenergic, histaminergic and dopaminergic systems. Among such, atomoxetine has been widely used, although its mechanism of action is poorly understood. It is known that central nervous system histamine is closely associated with cognition and it was recently shown that both atomoxetine and methylphenidate enhance cortical histamine release in rats. To that end, the aim of our study was to investigate the effect of atomoxetine (2 mg/kg, intraperitoneally) on histamine release using the microdialysis technique in the spontaneously hypertensive rat (SHR), a suitable genetic model for ADHD. Our data confirmed that atomoxetine increases extracellular levels of histamine in the prefrontal cortex, a brain region that is implicated in the pathophysiology of ADHD. Given the tie between histamine neurotransmission and treatment of cognitive dysfunction, we also assessed the effects of atomoxetine on learning and memory as measured by the Morris water maze in SHR. The results indicated that atomoxetine significantly ameliorated performance in the Morris water maze, consistent with its histamine-enhancing profile. In conclusion, the current study provides further support for the notion that the therapeutic effect of atomoxetine could involve activation of histamine neurotransmission within the prefrontal cortex.Attention-deficit hyperactivity disorder (ADHD) is one of the most commonly seen chronic health conditions featured by mental disorders in school-aged children and is characterized by elevated, age-inappropriate levels of inattention, impulsivity and excessive motor activity [1,2]. In addition, ADHD children usually experience problems with cognitive impulsiveness that are sometimes defined as planning deficits, forgetfulness and poor management of time [3].Spontaneously hypertensive rats (SHR) are considered as an animal model of ADHD because they display hyperactivity, impulsivity, poorly sustained attention and deficits in the learning and memory processes [4][5][6]. Furthermore, substandard performance has been noted in SHRs in a number of paradigms commonly used to evaluate learning and memory, such as the Morris water maze [7,8], the radial-arm maze [9] and the two-way shuttle box avoidance task [10]. For this reason, SHRs have been recommended as a unique model to evaluate pharmacological agents with therapeutic potential for disorders of memory and attention [8].To date, the 'dopaminergic hypothesis' based on a dysregulation in dopaminergic neurotransmission, has been the most widely accepted theory for behavioural alterations in both ADHD patients and SHR rats. There is considerable evidence suggesting that ADHD patients have disturbances in dopamine uptake, storage and/or metabolism [11][12][13][14][15]. Furthermore, SHR, a suitable model for ADHD, displays reduced release of dopamine in the prefrontal corte...

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Involvement of Norepinephrine in the Control of Activity and Attentive Processes in Animal Models of Attention Deficit Hyperactivity Disorder

Cited by 62 publications

References 117 publications

(R)-N-Methyl-3-(3-125I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

(R)-N-Methyl-3-(3-125I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters

Atomoxetine Increases Histamine Release and Improves Learning Deficits in an Animal Model of Attention‐Deficit Hyperactivity Disorder: The Spontaneously Hypertensive Rat

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