The dopamine transporter and attention-deficit/hyperactivity disorder

被引:284
作者
Madras, BK
Miller, GM
Fischman, AI
机构
[1] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Neurochem, Southborough, MA 01772 USA
[2] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA
关键词
methylphenidate; atomoxetine; amphetamine; monoamine transporters; brain imaging; norepinephrine transporter;
D O I
10.1016/j.biopsych.2004.10.011
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The high incidence of attention-deficit/hyperactivity disorder (ADHD) and escalating use of ADHD medications present a compelling case for clarifying the pathophysiological and developing laboratory or radiologic tests for, ADHD. Currently, the majority of specific genes implicated in ADHD encode components of catecholamine signalling 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 dopamine transport by brain-region and drug-specific mechanisms, indirectly activating dopamine- and possibly norepinephrine-receptor studies 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 noradreneroic as well as dopaminergic neutrons.
引用
收藏
页码:1397 / 1409
页数:13
相关论文
共 166 条
[1]   PHENYLETHYLAMINERGIC MECHANISMS IN ATTENTION-DEFICIT DISORDER [J].
BAKER, GB ;
BORNSTEIN, RA ;
ROUGET, AC ;
ASHTON, SE ;
VANMUYDEN, JC ;
COUTTS, RT .
BIOLOGICAL PSYCHIATRY, 1991, 29 (01) :15-22
[2]  
BARKLEY RA, 2001, ADHD REPORT NONARCHI, V9
[3]   Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder [J].
Barr, CL ;
Xu, C ;
Kroft, J ;
Feng, Y ;
Wigg, K ;
Zai, G ;
Tannock, R ;
Schachar, R ;
Malone, M ;
Roberts, W ;
Nöthen, MM ;
Grünhage, F ;
Vandenbergh, DJ ;
Uhl, G ;
Sunohara, G ;
King, N ;
Kennedy, JL .
BIOLOGICAL PSYCHIATRY, 2001, 49 (04) :333-339
[4]   Is ADHD a risk factor for psychoactive substance use disorders? Findings from a four-year prospective follow-up study [J].
Biederman, J ;
Wilens, T ;
Mick, E ;
Faraone, SV ;
Weber, W ;
Curtis, S ;
Thornell, A ;
Pfister, K ;
Jetton, JG ;
Soriano, J .
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, 1997, 36 (01) :21-29
[5]  
Biederman J, 2002, J Atten Disord, V6 Suppl 1, pS7
[6]  
Biederman J, 1998, J CLIN PSYCHIAT, V59, P4
[7]   Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder [J].
Biederman, J ;
Spencer, T .
BIOLOGICAL PSYCHIATRY, 1999, 46 (09) :1234-1242
[8]   Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood [J].
Bolaños, CA ;
Barrot, M ;
Berton, O ;
Wallace-Black, D ;
Nestler, EJ .
BIOLOGICAL PSYCHIATRY, 2003, 54 (12) :1317-1329
[9]   Trace amines: Identification of a family of mammalian G protein-coupled receptors [J].
Borowsky, B ;
Adham, N ;
Jones, KA ;
Raddatz, R ;
Artymyshyn, R ;
Ogozalek, KL ;
Durkin, MM ;
Lakhlani, PP ;
Bonini, JA ;
Pathirana, S ;
Boyle, N ;
Pu, XS ;
Kouranova, E ;
Lichtblau, H ;
Ochoa, FY ;
Branchek, TA ;
Gerald, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (16) :8966-8971
[10]   Trace amine receptors as targets for novel therapeutics: legend, myth and fact [J].
Branchek, TA ;
Blackburn, TP .
CURRENT OPINION IN PHARMACOLOGY, 2003, 3 (01) :90-97