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The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder

The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder
The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder

Through neuromodulatory influences over fronto-striato-cerebellar circuits, dopamine and noradrenaline play important roles in high-level executive functions often reported to be impaired in attention-deficit/hyperactivity disorder (ADHD). Medications used in the treatment of ADHD (including methylphenidate, dextroamphetamine and atomoxetine) act to increase brain catecholamine levels. However, the precise prefrontal cortical and subcortical mechanisms by which these agents exert their therapeutic effects remain to be fully specified. Herein, we review and discuss the present state of knowledge regarding the roles of dopamine (DA) and noradrenaline in the regulation of corticostriatal circuits, with a focus on the molecular neuroimaging literature (both in ADHD patients and in healthy subjects). Recent positron emission tomography evidence has highlighted the utility of quantifying DA markers, at baseline or following drug administration, in striatal subregions governed by differential cortical connectivity. This approach opens the possibility of characterizing the neurobiological underpinnings of ADHD (and associated cognitive dysfunction) and its treatment by targeting specific neural circuits. It is anticipated that the application of refined and novel positron emission tomography methodology will help to disentangle the overlapping and dissociable contributions of DA and noradrenaline in the prefrontal cortex, thereby aiding our understanding of ADHD and facilitating new treatments.

Attention-deficit/hyperactivity disorder, dopamine, frontostriatal circuits, nigrostriatal projections, noradrenaline, positron emission tomography
0006-3223
e145-e157
Del Campo, Natalia
16cfa0d6-12bd-41d1-8ae7-32e6eddc3f60
Chamberlain, Samuel R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Sahakian, Barbara J.
e689cd5c-b84f-4503-86ca-7526cf340121
Robbins, Trevor W.
20dd57dd-dbf3-4aaa-b7ba-bb4387ffcbc7
Del Campo, Natalia
16cfa0d6-12bd-41d1-8ae7-32e6eddc3f60
Chamberlain, Samuel R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Sahakian, Barbara J.
e689cd5c-b84f-4503-86ca-7526cf340121
Robbins, Trevor W.
20dd57dd-dbf3-4aaa-b7ba-bb4387ffcbc7

Del Campo, Natalia, Chamberlain, Samuel R., Sahakian, Barbara J. and Robbins, Trevor W. (2011) The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder. Biological Psychiatry, 69 (12), e145-e157. (doi:10.1016/j.biopsych.2011.02.036).

Record type: Review

Abstract

Through neuromodulatory influences over fronto-striato-cerebellar circuits, dopamine and noradrenaline play important roles in high-level executive functions often reported to be impaired in attention-deficit/hyperactivity disorder (ADHD). Medications used in the treatment of ADHD (including methylphenidate, dextroamphetamine and atomoxetine) act to increase brain catecholamine levels. However, the precise prefrontal cortical and subcortical mechanisms by which these agents exert their therapeutic effects remain to be fully specified. Herein, we review and discuss the present state of knowledge regarding the roles of dopamine (DA) and noradrenaline in the regulation of corticostriatal circuits, with a focus on the molecular neuroimaging literature (both in ADHD patients and in healthy subjects). Recent positron emission tomography evidence has highlighted the utility of quantifying DA markers, at baseline or following drug administration, in striatal subregions governed by differential cortical connectivity. This approach opens the possibility of characterizing the neurobiological underpinnings of ADHD (and associated cognitive dysfunction) and its treatment by targeting specific neural circuits. It is anticipated that the application of refined and novel positron emission tomography methodology will help to disentangle the overlapping and dissociable contributions of DA and noradrenaline in the prefrontal cortex, thereby aiding our understanding of ADHD and facilitating new treatments.

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More information

Accepted/In Press date: 15 February 2011
e-pub ahead of print date: 6 May 2011
Published date: 15 June 2011
Keywords: Attention-deficit/hyperactivity disorder, dopamine, frontostriatal circuits, nigrostriatal projections, noradrenaline, positron emission tomography

Identifiers

Local EPrints ID: 492922
URI: http://eprints.soton.ac.uk/id/eprint/492922
ISSN: 0006-3223
PURE UUID: 98c05df7-95ca-46a2-a279-2790d1f172ed
ORCID for Samuel R. Chamberlain: ORCID iD orcid.org/0000-0001-7014-8121

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Date deposited: 20 Aug 2024 16:48
Last modified: 21 Aug 2024 01:59

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Contributors

Author: Natalia Del Campo
Author: Samuel R. Chamberlain ORCID iD
Author: Barbara J. Sahakian
Author: Trevor W. Robbins

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