Regulation Of Mood And Behavior By Glutamate And Its NMDA Receptors In The Nucleus Accumbens Under Depressive Conditions

Depression is a mental disease of high incidence in the community population. The current study manifests that depression occurrence has the relationship with the social environment. Many kinds of stress in social life can produce psychological pressure to the individuals, and the long-term accumulation of psychological pressure is one of the reasons for the personal depression.Glutamate as a neurotransmitter, widely exist in the central nervous system. Many studies have shown that there is a close link between glutamate and depression. With regard to the study of glutamate and depression, the NMDA receptor is most studied.The study also showed that the NMDA receptor NR2B subunit of glutamate and dopamine receptor could interact with each other.Nucleus accumbens(NAc) is a kind of nerval nuclear group which has a close relationship with emotion and behavior. It accepts multiple projection from many brain areas, glutamate, dopamine and other neurotransmitters commonly regulate the NAc. The neurons in NAc were mainly composed of GABA neurons (MSN), it has both glutamate receptors and dopamine receptors. Studies have showed that antidepressant drugs can increase the function of D2 receptors in the nucleus accumbens, while the depression model of "maternal deprivation" mices manifests that D2 receptor mRNA level in NAc is decreased. In recent years, many studies have shown that NAc is closely related to the occurrence of depression. However, previous studies have paid more attention to the DA in NAc, and the functions of glutamate and its receptors on depression have not been reported. Therefore, it is helpful for us to further understand the mechanism of depression in the study of the role of NMDA receptors in the occurrence depression like behavior in NAc.The experiment was based on the establishment of chronic unpredictable mild stress (CUMS) model and micro-injection of glutamate NMDA receptor agonist NMDA and inhibitor MK-801 in the region of NAc. We need do the behavior test to get the data of behaviors, high performance liquid chromatography (HPLC) to know the levels of glutamate. Western blot to detect the level of NR2B subunit of NMDA receptor and dopamine D2 receptor. The experimental results are as follows:1.Compared with the normal control group, CUMS rats showed a significant depressive-like behavior,like anhedonia and decrease of exploration. The level of glutamiate in NAc was significantly increased. The expression level of NR2B subunit did not change significantly.2.compared with the CUMS group rats, NAc injection of MK-801 in normal rats did not affect the animals' behavior,3.NAc micro injection of MK-801 can improve the depressive-like behavior induced by CUMS, and can significantly reduce the level of glutamate,and reach the normal level, and NR2B expression also decreased.4.NMDA could induce depression-like behavior on normal rats. Glutamate concentration was inccreased in NAc.5. Stress or injection of NMDA and MK-801 had no significant effect on dopamine D2 receptor.The results showed that NAc and NMDA receptors were involved in the occurrence of depressive like behavior. The mechanism is mainly the interaction between glutamate and NMDA receptor, leading to the increase of glutamate and NMDA receptor's activation. NMDA receptor activation on NAc was a positive feedback to regulate the level of glutamate. The disorder of glutmate systerm could lead to depression.Glutamate and NMDA receptor do not regulate the expression of D2 receptor.