Reduced anxiety and depression-like behaviors in mice lacking GABA transporter subtype 1

Guoxiang Liu, Guo Qiang Cai, You Qing Cai, Zhe Jin Sheng, Jie Jiang, Zhengtong Mei, Zhu Gang Wang, Lihe Guo, Jian Fei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


γ-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.

Original languageEnglish (US)
Pages (from-to)1531-1539
Number of pages9
Issue number7
StatePublished - Jul 2007


  • Anxiety
  • Depression
  • GABA transporter 1
  • Knockout mouse

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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