Reduced anxiety and depression-like behaviors in mice lacking GABA transporter subtype 1.
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.
Liu
Guo-Xiang
GX
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.
Cai
Guo-Qiang
GQ
Cai
You-Qing
YQ
Sheng
Zhe-Jin
ZJ
Jiang
Jie
J
Mei
Zhengtong
Z
Wang
Zhu-Gang
ZG
Guo
Lihe
L
Fei
Jian
J
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009483:Neuropsychological Tests; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D050485:GABA Plasma Membrane Transport Proteins; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D003345:Corticosterone