Enhancement Effects Of Apelin-13 On Conditioned Fear Extinction In Rats

[Backgroud and Objective] Fear is an adaptive response that has evolved to provide protection from potential harm in the environment.But when fear is excessive and disproportionate to the situation,it could lead to the development of an anxiety disorders.According to The World Health Organization predicts that anxiety and depression disorders will become the second biggest burdensome illnesses in the word by 2020.Therefore,it is of great significance to understand and prevent the anxiety disorder caused by the fear.Fear extinction is a good candidate model that extensively used to study anxiety disorders.Apelin-13,as an endogenous neuropeptide,has recently been considered to regulate learning and memory and participate in the process of fear conditioning.It has been recently reported that apelin-13 has an anti-general anxiety effect,but the effect on acquired anxiety is still unknown.The purpose of this study was to investigate whether apelin-13 could promote the extinction of conditioned fear memory and relieve the symptoms of acquired anxiety in rats.[Methods] We adopt the classic conditional fear extinction paradigm of Pavlov.All rats habituate the training cases for 30 min on day 1,then the fear conditioning training phase were performed on day 2.All rats received once apelin-13(3 μg/6 μg)/vehicle i.c.v injection 23.5 hours after fear cnditioning,the extinction training and testing were conducted 0.5 and 24 hours after the drug injection.We first examined the effects of apelin-13 on the cued conditioned fear extinction in rats.And then we discussed the effects apelin-13 on contextual extinction.Finally,we further explored the effects of apelin-13 on nonspecific responses of rats,including the effects of the apelin-13 on the unconditioned rigidity reaction and locomotor activity of rats.[Results] Compared with the vehicle group,Apelin-13(3 μg)and Apelin-13(6 μg)group of rats showed significantly lower freezing time during the cued conditional fear extinction training phase.Apelin-13 groups also presented significantly lower percent of freezing during extinction testing phase.There was no significant difference in extinction rate within extinction training and testing.Therefore,apelin-13 significantly enhanced the extinction of long-term cued fear extinction,but had no effect on short-term cued fear extinction.During contextual fear extinction phase,Apelin-13(3 μg)and Apelin-13(6 μg)group of rats showed significantly lower freezing percent compared with the vehicle group during extinction training and testing.There was a significant difference in extinction ratio between groups within extinction training session.Thus,apelin-13 significantly enhanced the contextual short-term fear extinction memory,and promoted the conversion of short-term extinction memory to long-term extinction memory.Compared with the solvent group,Apelin-13(3 μg)and Apelin-13(6 μg)group of rats had no significant effects on nonspecific responses of rats.Hence,the enhancement effects of apelin-13 on the extinciton of cued and contextual conditional fear memory was not caused by the effect of nonspecific responses of rats.[Conclusion] Apelin-13 enhanced the extinction of cued and contextual conditioning fear memory in rats.