The Role Of Nociceptin In Novel Object Recognition Memory And The Undelying Mechanisms

ObjectivesN/OFQ(nociceptin/orphanin FQ),an endogenous ligand of the opioid receptor-like 1 receptor(ORL1,also known as NOPR),is widely distributed in vivo.N/OFQ regulats multiple physiological functions,such as nociception,food intake,cardiovascular function,stress,anxiety and depression.N/OFQ and its receptors are widely distributed in the nervous system,and play an important role in the regulation of spatial,fear and object recognition memories.N/OFQ receptors are highly distributed in the perirhinal cortex,which is a key brain area involved in modulating novel object recognition(NOR)memory.However,whether N/OFQ in the perirhinal cortex could regulate NOR memory was still unknown.Moreover,it remains unclear at what stage(acquisition,consolidation,and recall)are regulated by N/OFQ in NOR test.Therefore,in the present study,we will investigate the role of N/OFQ in NOR memory acquisition,consolidation,retrieval phases and whether N/OFQ in the perirhinal cortex could regulate NOR memory.Methods1.Cannula were implanted into lateral ventricle or bilateral perirhinal cortex,and whether the injection sites were in the correct position was judged by HE stain after the behavioral experiment.2.NOR memory was compared between N/OFQ-treated mice and vehicle-treated mice in NOR task,which based on the animals' spontaneous preference for the novel object.3.N/OFQ and vehicle were injected intracerebroventricularly(i.c.v.)before training,after training or before test phase to study the role of N/OFQ in NOR memory acquisition,consolidation and retrieval phases.4.Nphe,an antagonist of N/OFQ,was injected i.c.v before training phase of NOR task to study the mechanism of N/OFQ.5.N/OFQ(0.1 and 0.3nmol/side)and vehicle were injected into bilateral perirhinal cortex before training phase to study whether N/OFQ could modulate NOR memory in the perirhinal cortex.6.Qpen field test was conducted after injecting N/OFQ into the lateral ventricle and bilateral olfactory pericortex of mice,to investigate whether N/OFQ would affect motor ability and thus interfere with the results of new object recognition and memory.Results1.N/OFQ(0.3 and 1nmol)and vehicle were injected i.c.v.before training phase,the DI of each group did not show significant difference during the training phase.However,the DI of the vehicle-treated mice were significantly dose-dependent higher than that of the N/OFQ-treated miceduring the test phase.These results suggest that i.c.v.injection of N/OFQ before training phase dose-dependent impairs NOR memory.2.N/OFQ(1 and 3nmol)and vehicle were injected i.c.v.after training phase,and the DI of each group did not show significant difference during the training and test phases.These results suggest that i.c.v.injection of N/OFQ after training phase does not affect NOR memory consolidation.3.N/OFQ(1 nmol)and vehicle were injected i.c.v.before test phase,and the DI of each group did not show significant difference during the training and test phases.These results suggest that i.c.v.injection of N/OFQ before test phase does not affect NOR memory recall.4.[Nphe1]N/OFQ(1-13)NH2(Nphe)is a selective NOP receptor antagonist.The amnesia effect of N/OFQ(1 nmol,icv)could be prevented by pre-treatment with 10 nmol Nphe.Suggesting N/OFQ impairs NOR memory via activation the NOP receptors.5.N/OFQ(0.1 and 0.3nmol/side)and vehicle were injected into the bilateral perirhinal cortex before the training phase,the DI of each group did not show significant difference during the training phase.However,the DI of vehicle-treated mice were significantly higher than that of the N/OFQ-treated miceduring the testphase.Suggesting that the perirhinal cortex is a critical area for mediating the amnesic effect we observed after icv injection of N/OFQ.6.N/OFQ(1 and 3nmol)and vehicle were injected i.v.c.before the open field test.N/OFQ at the dose of 1 nmol induces a slight decrease in spontaneous locomotor activity and N/OFQ at the dose of 3 nmol induces a significant motor inhibitory effect.The bilateral perirhinal cortex infusion of N/OFQ(0.3 nmol/side)did not affect the spontaneous locomotor activity of mice.Suggesting that the amnesic effect of N/OFQ is not influence by its motor inhibitory effect.ConclusionsIn conclusion,the results from our present study demonstrated that the perirhinal cortex is a crucial area for mediating the novel object recognition of N/OFQ,and N/OFQ in the perirhinal cortex impairs NOR memory.In addition,N/OFQ functions by activating the N/OFQ receptor and impairs NOR memory specificity,especially during the acquisition phase,but not consolidation and retrieval phase.