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 methylp...
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| Published in | Biological psychiatry (1969) Vol. 69; no. 12; pp. e145 - e157 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
15.06.2011
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| Subjects | |
| Online Access | Get full text |
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| 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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| AbstractList | 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. 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.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. |
| Author | del Campo, Natalia Robbins, Trevor W. Sahakian, Barbara J. Chamberlain, Samuel R. |
| Author_xml | – sequence: 1 givenname: Natalia surname: del Campo fullname: del Campo, Natalia email: nd290@cam.ac.uk organization: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom – sequence: 2 givenname: Samuel R. surname: Chamberlain fullname: Chamberlain, Samuel R. organization: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom – sequence: 3 givenname: Barbara J. surname: Sahakian fullname: Sahakian, Barbara J. organization: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom – sequence: 4 givenname: Trevor W. surname: Robbins fullname: Robbins, Trevor W. organization: Department of Experimental Psychology, University of Cambridge, Cambridge, United Kingdom |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21550021$$D View this record in MEDLINE/PubMed |
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| Keywords | noradrenaline Attention-deficit/hyperactivity disorder positron emission tomography dopamine nigrostriatal projections frontostriatal circuits |
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| SubjectTerms | Animals Attention Deficit Disorder with Hyperactivity - diagnostic imaging Attention Deficit Disorder with Hyperactivity - drug therapy Attention Deficit Disorder with Hyperactivity - physiopathology Attention-deficit/hyperactivity disorder Brain Mapping - methods Central Nervous System Stimulants - pharmacology Central Nervous System Stimulants - therapeutic use Cerebral Cortex - diagnostic imaging Cerebral Cortex - drug effects Cerebral Cortex - physiopathology Corpus Striatum - diagnostic imaging Corpus Striatum - drug effects Corpus Striatum - physiopathology dopamine Dopamine - physiology frontostriatal circuits Humans Neural Pathways - diagnostic imaging Neural Pathways - drug effects Neural Pathways - physiopathology nigrostriatal projections noradrenaline Norepinephrine - physiology positron emission tomography Positron-Emission Tomography - methods Prefrontal Cortex - diagnostic imaging Prefrontal Cortex - drug effects Prefrontal Cortex - physiopathology Psychiatry |
| Title | The Roles of Dopamine and Noradrenaline in the Pathophysiology and Treatment of Attention-Deficit/Hyperactivity Disorder |
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