Document Detail


Reduced anxiety and depression-like behaviors in mice lacking GABA transporter subtype 1.
MedLine Citation:
PMID:  17164814     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gamma-aminobutyric acid (GABA) transporter subtype 1 (GAT1), which transports extracellular GABA into presynaptic neurons, plays an important regulatory role in the function of GABAergic systems. However, the contributions of the GAT1 in regulating mental status are not fully understood. In this paper, we observed the behavioral alterations of GAT1 knockout (GAT1(-/-)) mice using several depression- and anxiety-related models (eg, the forced-swimming test and the tail-suspension test for testing depression-related behaviors; the open-field test, the dark-light exploration test, the emergence test, and the elevated plus maze (EPM) test for anxiety-related behaviors). Here we found that GAT1(-/-) mice showed a lower level of depression- and anxiety-like behaviors in comparison to wild-type mice. Furthermore, GAT1(-/-) mice exhibited measurable insensitivity to selected antidepressants and anxiolytics such as fluoxetine, amitriptyline, buspirone, diazepam, and tiagabine in the tail-suspension test and/or the EPM test. Moreover, the basal level of corticosterone was found to be significantly lower in GAT1(-/-) mice. These results showed that the absence of GAT1 affects mental status through enhancing the GABAergic system, as well as modifying the serotonergic system and the hypothalamic-pituitary-adrenal (HPA) activity in mice.
Authors:
Guo-Xiang Liu; Guo-Qiang Cai; You-Qing Cai; Zhe-Jin Sheng; Jie Jiang; Zhengtong Mei; Zhu-Gang Wang; Lihe Guo; Jian Fei
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-12-13
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  32     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-14     Completed Date:  2007-08-31     Revised Date:  2011-05-18    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1531-9     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Model Organism Research Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Anxiety Agents / pharmacology
Antidepressive Agents / pharmacology
Anxiety Disorders / genetics,  metabolism*,  physiopathology
Behavior, Animal / physiology
Brain / metabolism*,  physiopathology
Brain Chemistry / genetics
Corticosterone / blood,  secretion
Depressive Disorder / genetics,  metabolism*,  physiopathology
Drug Resistance / genetics
Female
GABA Plasma Membrane Transport Proteins / deficiency,  genetics*
Hypothalamo-Hypophyseal System / metabolism,  physiopathology,  secretion
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neuropsychological Tests
Serotonin / metabolism
Stress, Psychological / metabolism,  physiopathology
gamma-Aminobutyric Acid / metabolism*
Chemical
Reg. No./Substance:
0/Anti-Anxiety Agents; 0/Antidepressive Agents; 0/GABA Plasma Membrane Transport Proteins; 50-22-6/Corticosterone; 50-67-9/Serotonin; 56-12-2/gamma-Aminobutyric Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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