Abstract
The spinal GABAergic system is reported to contribute to antinociceptive effects by activation of 5-HT3 receptors. The purpose of the present experiments is to elucidate synaptic functions of 5-HT3 receptors on GABAergic neurons in the spinal cord. Mice were anesthetized with pentobarbital. The spinal cord was removed and sectioned into 350 μm transverse slices. Under visual control using an infrared DIC microscope, whole-cell voltage clamp recordings at -70 mV were made from neurons located in the superficial dorsal horn. 2-Me-5-HT, a selective 5-HT3 receptor agonist, was applied by local perfusion using another glass pipette placed by the recorded neuron. The neurons, which showed postsynaptic inward currents induced by 2-Me-5-HT, were sampled for single cell reverse transcription-polymerase chain reaction (RT-PCR) analysis using primers specific for GABA-synthesizing enzyme GAD67. The analysis showed that GAD67 mRNA was detected in a part of the neurons. Furthermore, in the presence of tetrodotoxin, miniature inhibitory postsynaptic currents (mIPSCs) mediated by GABAA receptors were recorded. 5-Me-5-HT significantly increased the frequency of the GABAergic mIPSC without affecting their amplitude. These findings provide sound evidence that 5-HT3 receptors located at the presynaptic terminals and somatic membrane control the release of GABA and might contribute to the modulation of nociception in the superficial dorsal horn. [J Physiol Sci. 2008;58 Suppl:S133]
