CELL-PERMEABLE SCAVENGERS OF SUPEROXIDE PREVENT LONG-TERM POTENTIATION IN HIPPOCAMPAL AREA CA1

Long-term potentiation (LTP) in hippocampal area CA1 is generally depe ndent on N-methyl-D-aspartate (NMDA) receptor activation. Reactive oxy gen species (ROS), including superoxide, are produced in response to N MDA receptor activation in a number of brain regions, including the hi pppocampus. In this study, two cell-permeable manganese porphyrin comp ounds that mimic superoxide dismutase (SOD) were used to determine whe ther production of superoxide is required for the induction of LTP in area CA1 of rat hippocampal slices. Incubation of hippocampal slices w ith either Mn(III) tetrakis (4-benzoic acid) porphprin (MnTBAP) or Mn( III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP) prevented the i nduction of LTP. Incubation of slices with either light-inactivated Mn TBAP or light-inactivated MnTMPyP had no effect on induction of LTP. N either MnTBAP nor MnTMPyP was able to reverse preestablished LTP. Thes e observations suggest that production of superoxide occurs in respons e to LTP-inducing stimulation and that superoxide is necessary for the induction of LTP.