Protein kinase Mζ inhibitor.

ZIP, or Zeta inhibitory peptide, is a cell permeable pseudo-substrate inhibitor of protein kinase Mζ (PKMζ), a constitutively active, atypical PKC isozyme involved in LTP maintenance. ZIP selectively blocks PKMζ induced synaptic potentiation in hippocampal slices in vitro and is widely used to investigate memory in a variety of learning tasks, including spatial sensitization, pain sensitization, fear-associated memories, conditioned taste aversion and development of locomotor sensitization in rodents. However, LTP and LTM are unaffected in both constitutive and conditional PKMζ knock-out mice, yet both are still impaired by ZIP application, suggesting another mechanism of action which may involve ionotropic glutamate AMPA receptors (AMPARs).

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