Biomedical subjects

Guo-Xiang Liu

Publications and source records attributed to Guo-Xiang Liu.

3 recordsLinked to original sources

PubMed2007

Reduced aggression in mice lacking GABA transporter subtype 1.

Dysregulation of the brain GABAergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central GABAergic activity, dysfunction of the GABA transporter subtype 1 (GAT1) represents a potential mechanism mediating pathologic aggression. We provide evidence that GAT1-/- mice and GAT1+/- mice exhibit lower aggressive behavior both in home cage resident-intruder test and neutral arena resident-intruder test, compared to wild-type mice (GAT1+/+). The pharmacologic effects of the GAT1 inhibitor, tiagabine and the GABA(A) receptor antagonist, bicuculline have been assessed in GAT1+/+ mice: tiagabine inhibits attacks but bicuculline induces attacks. Compared to GAT1+/- and +/+ mice, the GAT1-/- mice displayed a normal circadian pattern of home cage activity, but more activity overall. Meanwhile, reduced testosterone concentration was found in GAT1-/- mice compared to GAT1+/+ mice but not in GAT1+/+ mice treated with tiagabine, suggesting that testosterone is not directly involved in GAT1 mediated aggressive behavior regulation. These results showed that GAT1 is an important target involved in the regulation of aggressive behavior in mice, and long-term dysfunction of GAT1 may also result in the alteration of testosterone secretion.

Aggression↗

PubMed2006

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.

Animals↗

PubMed2006

Mice with genetically altered GABA transporter subtype I (GAT1) expression show altered behavioral responses to ethanol.

It is widely accepted that the GABAergic system plays an important role in the action of ethanol in vivo. GABA transporter subtype 1 (GAT1) constructs high affinity reuptake sites in the CNS and regulates GABAergic transmissions. In this study, mice lacking the GAT1 were developed by homologous recombination. Both hetero- and homozygous GAT1 mutant mice were tested for ethanol, saccharin or quinine consumption, ethanol-conditioned place preference, ethanol-conditioned taste aversion, ethanol-simulated motor activity, and ethanol-induced sedation/hypnosis. The GAT1(-/-) mice showed decreased ethanol aversion and ethanol reward, and insensitivity to both the sedative/hypnotic and the motor stimulant effects of ethanol, along with increased avoidance of quinine preference and consumption. GAT1(+/-) mice showed significantly increased consumption of ethanol and saccharin, however, enhanced the rewarding and preference effect of ethanol, increased avoidance of quinine, and higher sensitivity to the motor stimulant effect of ethanol. These results demonstrate that GAT1, perhaps in a bi-directional way, modulates some behavioral effects of ethanol. The GAT1 mutant mice provided us a very useful model to investigate the mechanisms of ethanol action in vivo.

Analgesics, Non-Narcotic↗