1. ¹Laboratory 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
2. ²Graduate School of Chinese Academy of Sciences, Beijing, China
3. ³Shanghai Nan Fang Model Organism Research Center, Pu Dong, Shanghai, China
4. ⁴Model Organism Division, E-institutes of Shanghai Universities, Shanghai Jiao Tong University, Shanghai, China

Correspondence: Dr J Fei, Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Model Organism Research Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, No 7 Building, 319 Yue Yang Road, Shanghai 200031, China. Tel: +86 21 54920376; Fax: +86 21 58951005; E-mail: jfei@sibs.ac.cn

Received 30 March 2006; Revised 29 September 2006; Accepted 2 October 2006; Published online 13 December 2006.

Abstract

-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.