Mouse ¦Ã-aminobutyric Acid Transporter Subtype I (gat1) And Pain

The present study focused on the involvement of y -aminobutyric acid transporter I (GATl) in pain. We found that GAB A uptake was increased in mouse spinal cord both 20 min and 120 min after formalin injection and in mouse brain 120 min, but not 20 min after formalin injection, which indicate that GATl may play a role in the process of pain, we first used two kinds of GATl overexpressing transgenic mice (under the control of a CMV promoter or a NSE promoter) to examine the nociceptive responses in these mice. In the thermal, formalin and acetic acid assays, both kinds of transgenic mice displayed significant hyperalgesia after nociceptive stimuli. To further study the effects of GATl on pain, we constructed GATl knockout mice, RT-PCR and GABA uptake experiments showed that there is a lack of expression and function of GATl in our homogenous knockout mice. And this kind of knockout exhibited significant analgesia. Besides, the antinociceptive effects of GATl selective inhibitors were examined using assays of thermal (tail-flick) and chemical nociception (formalin and acetic acid) in C57BL/6J mice. The GATl selective inhibitors, ethyl nipecotate and NO-711, exhibited significant antinociceptive effects in these nociceptive assays. In addition, v- opioid receptor antagonist naloxone had no influence on nociceptive responses in wild-type and transgenic mice overexpressing GATl, while baclofen, an inhibitor of GABAe, can inhibit GABA uptake in the brain induced by formalin. These results indicate that GATl is involved in the regulation of pain processes, and point to the possibility of developing analgesic drugs that target GATl other than opioid receptors.