Publication Date:
1999-01-15
Description:
The mechanism by which psychostimulants act as calming agents in humans with attention-deficit hyperactivity disorder (ADHD) or hyperkinetic disorder is currently unknown. Mice lacking the gene encoding the plasma membrane dopamine transporter (DAT) have elevated dopaminergic tone and are hyperactive. This activity was exacerbated by exposure to a novel environment. Additionally, these mice were impaired in spatial cognitive function, and they showed a decrease in locomotion in response to psychostimulants. This paradoxical calming effect of psychostimulants depended on serotonergic neurotransmission. The parallels between the DAT knockout mice and individuals with ADHD suggest that common mechanisms may underlie some of their behaviors and responses to psychostimulants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gainetdinov, R R -- Wetsel, W C -- Jones, S R -- Levin, E D -- Jaber, M -- Caron, M G -- MH-40159/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1999 Jan 15;283(5400):397-401.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute Laboratories, Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9888856" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Attention Deficit Disorder with Hyperactivity/drug
;
therapy/physiopathology/psychology
;
Behavior, Animal/drug effects
;
Carrier Proteins/antagonists & inhibitors/drug effects/genetics/metabolism
;
Central Nervous System Stimulants/*pharmacology
;
Corpus Striatum/*metabolism
;
Dopamine/metabolism/physiology
;
Dopamine Plasma Membrane Transport Proteins
;
Fluoxetine/pharmacology
;
Humans
;
Hyperkinesis/*drug therapy/physiopathology/psychology
;
Maze Learning
;
Membrane Glycoproteins/drug effects/metabolism
;
*Membrane Transport Proteins
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Motor Activity/drug effects
;
*Nerve Tissue Proteins
;
Norepinephrine Plasma Membrane Transport Proteins
;
Serotonin/metabolism/*physiology
;
Serotonin Plasma Membrane Transport Proteins
;
Serotonin Uptake Inhibitors/pharmacology
;
*Symporters
;
*Synaptic Transmission
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
