Hippocampal Dopamine D1 Receptor Activation And Inhibition Of Glutamate-mediated Rat Chronic Stress-induced Depression

Depression belongs to a mental disorder. Its typical character is low spirits. Stress is an unspecific adaptive response when people or animals are confronted with various stimuluses. Social stress, such as the quickened social rhythm, increasingly furied work competition, makes people bear more and more mental burdens. Therefore, stressful life events is closely related to the incidence of depression. However, the exact mechanism underlying depression development is still elusive. The present study was to investigate the role and relationship of dopamine D1 receptors, glutamate. N-methyl-D-aspartic acid (NMDA) receptor and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor in depression induced by chronic unpredictabil mild stress (CUMS). CUMS-induced depression model was established in Sprague-Dawley rats, intra-hippocampal microinjections of D1 dopamine receptor agonists SKF38393, non-competitive NMDA receptor antagonist MK-801and AMPA receptor antagonist NBQX were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of weight changes, sucrose preference test, open-field test and suspended test. The concentration of glutamic acid and the expression of its receptors' subunits were detected by HPLC and western blot respectively. The resuts are as follows:1, Compare with the Control group, the behavioural ability of the CUMS rats significantly depressed, the concentration of glutamic acid increse (n=6,P<0.05). the expressions of NMDA receptor (NR1) and AMPA receptor (GluR2/3) decrese (n=8,P<0.01) in hippocampus.2, we gave intra-hippocampal injections of an dopamine D1 receptor inhibitor (SKF383930). which suppressed depression-like behavioral changes induced by CUMS. the concentration of glutamic acid decrese (n=6,P<0.01). the expressions of NMDA receptor (NR1) and AMPA receptor (GluR 2/3) increse (n=8,P<0.01) in hippocampus.3, Built CUMS model. then intra-hippocampal injections of MK-801 or NBQX and SKF38393. we find MK-801 could enhance the antidepressant effect of SKF38393. while NBQX weaken.These results suggest that agonists of Dl dopamine receptor could reduce the concentration of glutamic acid in hippocampal. and its antidepressant effect was mediated by AMPA receptor partially.