[Express] Effects of matrix metalloproteinase inhibitors on NMDA receptor and contribute to long-term potentiation in the anterior cingulate cortex of adult mice.

Matrix metalloproteinases (MMPs) have been suggested to contribute to long-term potentiation (LTP) and behavioral learning, and memory. In the dorsal horn of spinal cord, MMPs were reported to contribute to injury-related changes, and inhibitors of MMPs have been proposed as potential analgesics. However, it is unclear whether MMP inhibitors produce these effects by inhibiting the function of NMDA receptor (NMDAR), a key receptor for the induction of LTP. In the present study, we wanted to examine if MMP inhibitors affect NMDAR mediated excitatory postsynaptic currents (EPSCs) in the anterior cingulate cortex (ACC) of adult mice. Among different subtype inhibitors we used, we found that MMP-9 and MMP-2/9 inhibitors did not change NMDAR-mediated EPSCs. However, MMP-3 and broad-spectrum MMP inhibitors reduced the NMDAR-mediated EPSCs. Consistently, MMP-9 and MMP-2/9 inhibitors had no effected for NMDAR dependent LTP, but MMP-3 and broad-spectrum MMP inhibitors inhibited the induction of LTP. Our results suggest that MMP inhibitors may produce their effects by inhibiting NMDAR functions in central synapses.