Modulation Of Opioid μ Receptors In Learned Helpless Behavior

Helplessness and hopelessness caused by learned helplessness induce a series of complex physiological and psychological reactions,which often lead to cognitive,emotional and behavior changes,even induce serious neuropsychiatric problems such as anxiety disorder and depression.Helplessness and hopelessness feature prominently in the field of clinical studies and psychiatry on depression.Researchers believe that the individual’s uncontrollable sense of aversion or adverse environmental events is a key in the development of depressive symptoms.Research on this topic is an important opportunity for understanding depression.Appropriate animal models are important ways to research helplessness,and learned helplessness animal models are one of the earliest used animal models.Animals are generally put in an irritating enviroment that cannot be controlled or escaped,and then in an environment which can control or escape in the classic learned helpless animal model.The animals suffered from the irritating stimulus usually exhibit escape deficiency and produce anxiety-like or depression-like emotions.However,recently,the opinion that the escape deficiency of the learned helplessness animal model is caused by the learned helplessness has been challenged by some researchers.Because the animal’s escape deficiency was a natural respons or a passive acceptance to electric shock.In this study,we used a modified learned helplessness animal model that first allow animals to control or escape aversive stimuli,and then lose the control of aversive stimuli.The modified learned helplessness animal model(LOC)can induce animal’s emotional and behavioral changes by out of control over aversive events.In addition to regulating pain and addiction,opioid receptors also participate in cognitive activities such as learning and memory including spatial reference memory,conditioned fear memory,attention deficit,reward,value decision and so on.Studies have shown thatin healthy individuals,agonists of μ opioid receptors(μRs)can impair normal cognitive processes.In addition to participating in cognitive activities,μRs is also related to the regulation of emotional responses,especially anxiety and depression.Some researchers believe that the regulation of μRs is dynamic in negative emotions caused by laboratory conditions.As one of the animal models of depression,the learned helplessness animal model is often used for depression research.Some researchers have found that opioid agonists show different effects on animal escape deficiency in different stages of the model.There are three different stages in the modified learned helplessness animal model:escape behavior learning phase,evasion phase and test phase.Animals have different cognitive and emotional activities at different stages.Wheather μR regulate these three stages is still not clear.In order to explore the regulatory role of μRs on learned helplessness,this study uses drugs at different stages of the modified learned helplessness animal model.In the three stages of model,mice were systemic injected with μRs-specific antagonistβ-FNA.We uesd behavioral experiments such as shuttle box,forced swimming,elevated cross-maze experiment to observe animal behavior changes to investigate the functions of μRs in learned helplessness behaviors in mice.To reveal its possible neural mechanisms and provide new ideas for the treatment of depression in the future,conditioned neuronal μRs gene knockout mice were also used as experimental animals.The main results are as follows:(1)Blockage of μRs increases mice’s exploratory behavior during the evasion behavior phase.(2)Blockage of μRs reduces escape deficiency behavior and anxiety-like or depression-like mood in mice.(3)The absence of μRs on GABAergic neurons reduces the escape deficiency and depression-like emotions in mice with learning-extinction of escape behaviors,and increases the escape deficiency and depression-like emotions in mice without learning-extincton of escape behaviors.The above results indicate that μRs participates in the process of helplessness and plays a different role in various experiences of helplessness.