In The Occurrence Of Stress Depression, DA-D1R Regulates Mood And Behavior Through 5-HT And Its 1A Receptor Pathway

Recently,depression seriously endangers the physical and mental health of human beings.But the mechanism of depression is not entirely clear.People are facing more and more mental stress as society develops.It is time to figure out the pathogenesis and treatment of depression.The abnormal metabolism of 5-HT(5-hydroxytrytpamine)and its receptor which is the important monoamine transmitters may be the basic cause of depression.Antidepressants based on 5-HT play an important role in clinical treatment,but the effect of these drugs lags behind,and the effect of 30%of patients is not efficient.5-HTand its 5-HT1A receptor play a vital role in depression.Meanwhile,it is also suggested that the main cause of depression is not the decrease of 5-HT level,but may be caused by the dysregulation of 5-HT receptor.The dysregulation of dopamine system is closely related to depression.Earlier studies have found that depression may be associated with low extracellular DA levels.Parkinson rats by damaging dopaminergic neurons in the substantia nigra or PDD patients are accompanied by depression-like behavior.Dopamine receptor agonists can effectively ameliorate depressive symptoms in PDD patients,which is better than SSRIs.The decrease of dopamine in the brain may be an important reason of depression.The decrease of dopamine affects the 5-HT neurons and their pathways,which leads to depression.Glutaminergic neurons are the largest number of excitatory neurons in the brain.The glutamate system is the focus of psychologic research and may be the final integration pathway of antidepressant therapy.It is not clear whether the glutamate system is affected by 5-HT and its 1A receptor in depression and the antidepression by DA via D1 receptor.Depression was related to the dysfunction of prefrontal lobe,and the volume of mPFC decreased in depression patients.However,it is unclear whether the antidepressant effect of dopamine in mPFC is related to 5-HT pathway or whether it regulates Glu neurons through 5-HT system.In this research,we used a model of chronic unpredictable stress to study whether dopamine in mPFC affects 5-HT and its 5-HT1A receptor through D1R in stress and antidepression.Then regulate the glutamate system and play a key role.We adopted bilateral mPFC injection of D1 receptor agonist SKF38393 and 5-HTIAR antagonist WAY-100635,to detect the behavior test and the level of-5-HT,DA and the expression of 5-HT1AR.NR2B GluA2 in rats.The results are as follows:1.After 21 days of CUMS,depression-like behavior was observed in rats.The level of 5-HT in mPFC did not change significantly,but the level of DA decreased,the expression of 5-HT1AR decreased,the expression of NR2B increased and the expression of GluA2 decreased.2.Microinjection of dopamine DIR agonist SKF38393 into mPFC of CUMS rats has the antidepressant effect,5-HT level had no significant change,DA level increased,5-HT1AR expression upregulated,GluA2 expression increased,NR2B expression downregulated.3.The combined effect of dopamine DIR agonist SKF38393 and 5-HTlAR antagonist WAY-100635)could block the antidepressant effect of mPFC in CUMS rats.There was no significant change in 5-HT of CUMS rats,but the level of DA was increased,and the expression of NR2B was increased.The expression of GluA2 was decreased.The results suggest that the main cause of stress depression is the decrease of dopamine level in mPFC,which leads to the decrease of 5-HT system function.The effect of dopamine D1 receptor agonist SKF38393 is achieved by regulating glutamate NMDA and AMPA receptors through 5-HT1AR.