The effect of PKMζ inhibition on cocaine‐induced place preference and locomotor sensitization

Abstract

While many molecules have been implicated in the induction of a memory, less is known about the molecular mechanisms underlying the persistence of a memory. Protein kinase M ζ (PKMζ) has been demonstrated to be necessary for the maintenance of LTP, spatial memory and conditioned taste aversion. This study investigated whether PKMζ is also necessary for the maintenance of two addiction‐related memories, cocaine‐induced conditioned place preference (CPP) and locomotor sensitization. The role of PKMζ is typically examined by giving a single, region‐specific application of the PKMζ inhibitor, ζ inhibitory peptide (ZIP). The current study examined the effects of chronic PKMζ inhibition on the development of CPP and sensitization induced by cocaine (15 mg/kg, ip). ZIP was continuously delivered i.c.v. using an osmotic minipump throughout the six training sessions. Mice receiving ZIP during training showed reduced locomotor activity as compared to control mice. However, a sensitization test given while animals were not receiving ZIP revealed only a minor deficit that was not significant. Further, memory for CPP, tested off‐ZIP was not impaired. This suggests, while on‐ZIP, development and expression of sensitization are impaired, but off‐ZIP there was no deficit in memory for sensitization and place preference. This research was supported by NSF Graduate Research Fellowship (KKH), NIH grant DA020041 (SGA).