D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD
Low doses of psychostimulants produce beneficial behavioral effects in ADHD patients but the mechanisms underlying the response are not understood. Here we use the hyperactive mouse mutant coloboma to identify D2-like dopamine receptor subtypes that mediate the hyperactivity and response to amphetam...
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doaj-ce690493819740c1b67cd1c4b85c73d22021-03-20T04:58:29ZengElsevierNeurobiology of Disease1095-953X2010-01-01371228236D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHDXueliang Fan0Ming Xu1Ellen J. Hess2Departments of Pharmacology and Neurology, Emory University School of Medicine, 101 Woodruff Circle, Suite 6300 Atlanta, GA 30322, USADepartment of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USADepartments of Pharmacology and Neurology, Emory University School of Medicine, 101 Woodruff Circle, Suite 6300 Atlanta, GA 30322, USA; Corresponding author. Fax: +1 404 712 8576.Low doses of psychostimulants produce beneficial behavioral effects in ADHD patients but the mechanisms underlying the response are not understood. Here we use the hyperactive mouse mutant coloboma to identify D2-like dopamine receptor subtypes that mediate the hyperactivity and response to amphetamine; we have previously demonstrated that D1-like dopamine receptors are not involved. Targeted deletion of the D2, but not the D3 or the D4, dopamine receptor in coloboma mice eliminated the hyperactivity; depleting D2 dopamine receptors also restored the excess dopamine overflow that may drive the hyperactivity to normal concentrations. Similar to its effects on ADHD patients, amphetamine reduced the hyperactivity of coloboma mice. The D2 dopamine receptor-selective antagonist L-741,626, but not D3 or D4 dopamine receptor-selective antagonists, blocked the amphetamine-induced reduction in locomotor activity. Thus, the D2 dopamine receptor subtype mediates both the hyperactivity and response to amphetamine, suggesting a specific target for novel therapeutics in ADHD.http://www.sciencedirect.com/science/article/pii/S0969996109002861HyperactivitycolobomaD2 dopamine receptorD3 dopamine receptorD4 dopamine receptorAmphetamine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xueliang Fan Ming Xu Ellen J. Hess |
spellingShingle |
Xueliang Fan Ming Xu Ellen J. Hess D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD Neurobiology of Disease Hyperactivity coloboma D2 dopamine receptor D3 dopamine receptor D4 dopamine receptor Amphetamine |
author_facet |
Xueliang Fan Ming Xu Ellen J. Hess |
author_sort |
Xueliang Fan |
title |
D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD |
title_short |
D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD |
title_full |
D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD |
title_fullStr |
D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD |
title_full_unstemmed |
D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD |
title_sort |
d2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of adhd |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2010-01-01 |
description |
Low doses of psychostimulants produce beneficial behavioral effects in ADHD patients but the mechanisms underlying the response are not understood. Here we use the hyperactive mouse mutant coloboma to identify D2-like dopamine receptor subtypes that mediate the hyperactivity and response to amphetamine; we have previously demonstrated that D1-like dopamine receptors are not involved. Targeted deletion of the D2, but not the D3 or the D4, dopamine receptor in coloboma mice eliminated the hyperactivity; depleting D2 dopamine receptors also restored the excess dopamine overflow that may drive the hyperactivity to normal concentrations. Similar to its effects on ADHD patients, amphetamine reduced the hyperactivity of coloboma mice. The D2 dopamine receptor-selective antagonist L-741,626, but not D3 or D4 dopamine receptor-selective antagonists, blocked the amphetamine-induced reduction in locomotor activity. Thus, the D2 dopamine receptor subtype mediates both the hyperactivity and response to amphetamine, suggesting a specific target for novel therapeutics in ADHD. |
topic |
Hyperactivity coloboma D2 dopamine receptor D3 dopamine receptor D4 dopamine receptor Amphetamine |
url |
http://www.sciencedirect.com/science/article/pii/S0969996109002861 |
work_keys_str_mv |
AT xueliangfan d2dopaminereceptorsubtypemediatedhyperactivityandamphetamineresponsesinamodelofadhd AT mingxu d2dopaminereceptorsubtypemediatedhyperactivityandamphetamineresponsesinamodelofadhd AT ellenjhess d2dopaminereceptorsubtypemediatedhyperactivityandamphetamineresponsesinamodelofadhd |
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