Hippocampal knock down of NMDA receptor induces deficit of PPI

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The present experiment conformed to the Guidelines on the ethical use of laboratory animals of Kitasato University. Male Wistar rats were used. The NR1 hippocampal knockdown was performed by single injection of NR1 antisense-HVJ-liposome complex into the bilateral hippocampus of rats. The sustained downregulation of expression of NR1 by NR1-antisense was confirmed by western blot analysis. Western blot analysis demonstrated that the NR1-antisense treatment provided specifically the downregulation (about 30%) of NR1 expression in the hippocampus for more than a week. Firstly, it was shown that disruption of pre-pulse inhibition (PPI) was produced in the rats with antisense-induced hippocampal knockdown of NMDA receptor NR1 subunit (NR1). Next, we examined whether this disruption of PPI in NR1 knockdown rats was recovered by dopamine receptor antagonist haloperidol (HPD), to clarify the relation between glutamate dysfunction and dopamine hyperfunction. On the PPI test, application of moderate or high dose of HPD induced recovery from defective PPI in the rats with NR1 knockdown by antisense.