The Role Of Adrenergic α1 Receptor In Hippocampus In Chronic Stress-induced Depression-like Behavior

Depression is a chronic relapsing syndrome of emotional mainly clinical for mood disorders or affective disorder, which has a high incidence of harm. It has been shown that monoamine neurotransmitter and its receptor function may be the underlying causes of depression, and glutamic acid (Glu) and its receptors function may be an important reason for depression. The study found that the expression of alpha 1 adrenergic receptor was reduced in the central nervous system of patients,and activation of alpha 1 receptors can produce antidepressant effect, but the mechanism of antidepressant effect of alpha 1 receptors is not clear. The hippocampus is closely related to the occurrence of brain and depression, Some studies had indicated that the distribution of adrenergic alpha 1 receptors in the hippocampus CA1 and CA3 areas and the activation of alpha 1 receptors can make the release of glutamate less in the hippocampus. Some other studies also reported that the activation of alpha 1 receptors could increase the release of GABA and aminobutyric in spinal dorsal horn and hippocampus. However, there was no report about the relationship between the expression of alpha 1 receptor and depression, and its effect was not clear about Glu and GABA. Therefore, this study try to investigate adrenergic alpha 1 receptors expression changes in hippocampus of the chronic stress depression, and alpha 1 receptors regulate Glu and GABA levels and the expression of NMDA receptor and AMPA receptor in hippocampus, and to explore the relationships. Providing a new way to understand the mechanism of stress induced depression.In order to solve those problems, we established chronic unpredictable mild stress (CUMS) model of depression. Microinjecting alpha 1 receptors agonist Phenylephrine and alpha 1 receptors antagonist Prazosin into hippocampus in rats, we adapted several methods to investigate the way of alpha 1 receptors antidepressant effect in stress-induced, such as behavior test methods, high-performance liquid chromatography for detecting the level of neurotransmitter within hippocampus, and Western Blot for detecting the expression of alpha 1 receptors, NMDA receptors and AMPA receptors subunits within hippocampus to investigate the way of alpha 1 receptors antidepressant effect in stress-induced. The results were shown as followed:1. After the model of chronic and non predictable mild stress, rats did show a very significant depressive like behavior, increased the level of Glu, decreased the level of GABA. The expression of alpha 1 receptors, NMDA receptors’ subunits NR2B and AMPA receptors subunits (GluR2/3) decreased significantly within hippocampus in comparison with the control group.2. Depression like behavior induced by CUMS can be significantly improved by Microinjection of alpha 1 receptors agonist Phenylephrine in hippocampus and the level of Glu within hippocampus was decreased significantly. At the same time, the levels of GABA, the expression of NMDA receptors’subunits NR2B and AMPA receptors subunits (GluR2/3)were also increased.3. Microinjection of alpha 1 receptors antagonist Prazosin into hippocampus did not cause the rat depression like behavior, and Glu and GABA content and NMDA receptor NR2B subunit, AMPA receptor Glu2/3 subunit expression did not change significantly.The results indicated that chronic unpredictable mild stress can cause decreased of adrenergic alpha 1 receptors expression in hippocampus which lead to Glu release excessive, the expression of NMDA receptors’subunits NR2B and AMPA receptors’ subunits GluR2/3 decreased. At the same time, the level of GABA was decreased, which affected the balance of Glu and GABA, and induced the depression like behaviors.