Altered behavioral responses to noxious stimuli and fear in glutamate receptor 5 (GluR5)- or GluR6-deficient mice.

Different kainate receptor (KAR) subtypes contribute to the regulation of both excitatory and inhibitory transmission. However, no study has reported a role for KAR subtypes in behavioral responses to persistent pain and fear memory. Here we show that responses to capsaicin or inflammatory pain were significantly reduced in mice lacking glutamate receptor 5 (GluR5) but not GluR6 subunits. In classic fear-memory tests, mice lacking GluR6 but not GluR5 showed a significant reduction in fear memory when measured 3, 7, or 14 d after training. Additionally, synaptic potentiation was significantly reduced in the lateral amygdala of GluR6 but not GluR5 knock-out mice. Our findings provide evidence that distinct KAR subtypes contribute to chemical/inflammatory pain and fear memory. Selectively targeting different KAR subtypes may provide a useful strategy for treating persistent pain and fear-related mental disorders.