| Depression is a kind of mental illness with persistent unpleasant mind and cognitive dysfunction,which is difficult to cure and has a high incidence.It not only reduces the quality of individuals life,but also is a huge burden to the community.Therefore,it is very significance to study the pathogenesis of depression.Over the past years,accumulated studies have shown that:monoamine neurotransmitter and its receptor disorders may be the underlying causes of depression.While the dopaminergic system may play a key role in the development of depression,especially dopamine D2 receptor.The nucleus accumbens is an important nucleus in the emotional behavior loop,with a high level of dopamine and its D1,D2 receptors.Activity of the NAc is consistently reduced in major depression,but deep brain stimulation of this region can relieve depression.Activation of D2 receptor can inhibit the synthesis and release of dopamine,long-term stress will lead to reduce the level of dopamine.It can be seen that dopamine and its D2 receptors are involved in the stress and emotional behavior of rats.In addition,there is a certain relationship between dopamine and dendritic spines,and Kalirin-7 is a key factor in regulating the structure and function of-dendritic spines.However,in chronic unpredictable mild stress,whether the levels of dopamine and its D2 receptor changed,whether D2 receptor are involved in the development of stress-induced depression-like behavior by regulating dopamine levels,and the regulation of neuronal dendrites Spine Kalirin-7 also changed,whether the change is affected by dopamine and its D2 receptor are not clear.In order to answer these questions,we using the pharmacology approaches by microinjecting of D2R receptor agonist quinpirole and its antagonist eticlopride to the NAC,we detected behavioral changes by using behavior tests including sucrose preference test,open field test and tail suspension test.In addition,high-performance liquid chromatography was used to detect the level of dopamine in the NAC.The expression of D2R and Kalirin-7 in the NAC was detected by western blot.The results are as follows:1.Rats in the chronic unpredictable mild stress group showed depression-like behavior,with a decreased dopamine levels in the nucleus accumbens,the levels of D2 receptor and Kalirin-7 were significantly lower compared with the control group(p<0.01,p<0.05).2.Compared with the control group,the intra-NAC injection of D2 receptor agonist quinpirole can significantly increase depression and reduce the level of D2 receptor and Kalirin-7(p<0.01,p<0.05);Compared with CUMS group,injection D2 receptor did not change the level of D2 receptor and Kalirin-7(p>0.05).3.Injection of D2 receptor antagonists eticlopride suppressed depression-like behavioral and increased the level of D2 receptor and Kalirin-7(p<0.0 1,p<0.05);Compared with the control group,the intra-NAC injection of D2 receptor antagonists eticlopride did not change the level of D2 receptor and Kalirin-7.4.Compared with the CUMS group,the intra-NAC injection of dopamine significantly increased the body weight of rats(p<0.01),the rate of sucrose preference increased and the immobility time decreased,but no significant difference was found(p>0.05).From the above results,we conclude that:CUMS could successfully induce the depressive-like behavior of rats,and the occurrence of depressive-like behavior was related to the low level of dopamine,as well as the level of D2 receptor and Kalirin-7,the phosphorylation level of D2 receptor and its activity may be more critical.D2 receptor antagonists play an antidepressant role by upregulating dopamine levels,whereas DA effects of dendritic spines may be achieved by upregulating the expression of Kalirin-7.The study suggests that altering the dopamine level in the nucleus accumbens by the D2 receptor may further affect the expression of Kalirin-7 as one of the effective ways to treat depression. |
PDF Full Text Request