Cited by 394Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatment

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The Dopamine Transporter and Attention-Deficit/Hyperactivity Disorder

Madras, Bertha K., Miller, Gregory M., Fischman, Alan J.·2005·Biological Psychiatry

DOI 10.1016/j.biopsych.2004.10.011

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Abstract

The high incidence of attention-deficit/hyperactivity disorder (ADHD) and escalating use of ADHD medications present a compelling case for clarifying the pathophysiology of, and developing laboratory or radiologic tests for, ADHD. Currently, the majority of specific genes implicated in ADHD encode components of catecholamine signaling systems. Of these, the dopamine transporter (DAT) is a principal target of the most widely used antihyperactivity medications (amphetamine and methylphenidate); the DAT gene is associated with ADHD, and some studies have detected abnormal levels of the DAT in brain striatum of ADHD subjects. Medications for ADHD interfere with dopamine transport by brain-region- and drug-specific mechanisms, indirectly activating dopamine- and possibly norepinephrine-receptor subtypes that are implicated in enhancing attention and experiential salience. The most commonly used DAT-selective ADHD medications raise extracellular dopamine levels in DAT-rich brain regions. In brain regions expressing both the DAT and the norepinephrine transporter (NET), the relative contributions of dopamine and norepinephrine to ADHD pathophysiology and therapeutic response are obfuscated by the capacity of the NET to clear dopamine as well as norepinephrine. Thus, ADHD medications targeting DAT or NET might disperse dopamine widely and consign dopamine storage and release to regulation by noradrenergic, as well as dopaminergic neurons.

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Authors: Madras, B. K., Miller, G. M., & Fischman, A. J.
Affiliations: Harvard University (US)
Massachusetts General Hospital (US)
Corresponding author: Madras, Bertha K.
ORCID: Madras, Bertha K.
Miller, Gregory M.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2005-06
Volume: 57
Issue: 11
Pages: 1397-1409
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2004.10.011
OpenAlex: W2011083427
Cited by: 393
References: 166
Citations by year: 2026: 10 · 2025: 20 · 2024: 9 · 2023: 13 · 2022: 11 · 2021: 12 · 2020: 18 · 2019: 10 · 2018: 11 · 2017: 11 · 2016: 14 · 2015: 15 · 2014: 23 · 2013: 16 · 2012: 27
FWCI: 4.54
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Drug Abuse (DA 06303, R01DA011558, K05DA015305, DA15305, DA 11558)
National Center for Research Resources (RR00 168)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: dopamine transporter, attention deficit hyperactivity disorder, ADHD pathophysiology, catecholamine signaling, norepinephrine transporter, amphetamine, methylphenidate, striatum, dopamine, norepinephrine, ADHD medication, genetic susceptibility
MeSH terms: Adaptation, Physiological, Central Nervous System Stimulants, Animals, Attention Deficit Disorder with Hyperactivity, Diagnostic Imaging, Humans, Membrane Glycoproteins, Mutation, Nerve Tissue Proteins, Genetic Variation, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins, Vesicular Biogenic Amine Transport Proteins

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