Hypoalgesia in mice lacking GABA transporter subtype 1.
gamma-Aminobutyric acid (GABA) transporters play a key role in the regulation of GABA neurotransmission. We reported previously that overexpression of the GABA transporter subtype 1 (GAT1), the major form of the GABA transporter in the CNS, led to hyperalgesia in mice. In the present study, nociceptive responses of GAT1-knockout mice (GAT1(-/-)) were compared with those of heterozygous (GAT(+/-)) and wild-type (GAT(+/+)) mice by four conventional pain models (tail-immersion test, hot-plate test, acetic acid-induced abdominal constriction test, and formalin test). In addition, the analgesic effects of two GAT1-selective inhibitors, NO-711 and tiagabine, were examined in all three genotypes using the same four models. Our data demonstrated that GAT1 deficiency because of genetic knockout or acute blockade by selective inhibitors leads to hypoalgesia in mice. These results confirmed the crucial role of GAT1 in the regulation of nociceptive threshold and suggested that GAT1 inhibitors have the potential for clinical use in pain therapy.
Xu
Yin Fang
YF
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, SIBS, CAS, Shanghai, China.
Cai
You Qing
YQ
Cai
Guo Qiang
GQ
Jiang
Jie
J
Sheng
Zhe Jing
ZJ
Wang
Zhu Gang
ZG
Fei
Jian
J
D000818:Animals; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009557:Nipecotic Acids / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D000078308:Tiagabine
D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D009557:Nipecotic Acids; D010091:Oximes; C078793:NNC 711; D000078308:Tiagabine