| Stressors markedly influence central neurochemical and hormonal processes and thus play a pivotal role in the occurrence of depressive illnesses. As the center for stress response and the potential target for stressful provocation, hippocampus is becoming a focus in depression research. Although a large number of behavioral paradigms have been proposed as animal models of depression, only a few are considered as potentially useful research tools with sufficient validity. The most accepted one is chronic unpredictable mild stress rodent model, in which rats were subjected chronically and unpredictably to a variety of stressors including immersion in cold water, tail pinch, day and night reversed and so on.There are several theoretic mechanisms for depression, such as monoamine neurotransmitter imbalance theory, neural plasticity theory, but none of them can fully elucidate the formation of depression. Due to weakness of the antidepressant-like effect of monoamines, glutamate (Glu) and its receptors, especially N-methyl-D-aspartic acid (NMDA) receptor, and a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor are drawing closer attention in recent years. As an important isoform of5-HT receptor,1A receptor highly expressed in hippocampus. Generous pharmacology and cinical studies show,1A receptor is correlated with the development and therapy of major depressive disorder, anxiety and drug addiction.Kalirin is a multifunctional GEF in brain, and it is necessary for maintenance of dendritic spins and dendritic branches. The number of dendritic spins decreased significantly, even disappear in hippocampus in kalirin-7knock-out animals. There is studies indicate that2A receptor could induce the change of size and number of dentritic spins in PFC via kalirin-7.The present study was to investigate the expression and role of5-hydroxytryptamine receptor1A(5-HT1AR) and its relationship with NMDA receptor, AMPA receptor and kalirin-7in depression induced by chronic unpredictable mild stress (CUMS).CUMS induced depression model was established in Sprague-Dawley rats, intra-hippocampal micro injections of antagonist of1A receptor (WAY100635), and agonist of1A receptor (8-OH-DPAT) adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of weight changes, sucrose preference test, open-field test and tail suspension test. The expression of5-HT1AR and kalirin-7was detected by Western blot, the expression and phosphorylation of NMDA receptors’and AMPA receptors’subunits were detected by Western blot and Elisa, respectively.The results showed that, compared with CON/SAL group, CUMS rats showed depression-like behavioral changes, lower expressions of5-HT1AR and kalirin-7lower expressions and phosphorylation of AMPA receptor (GluR2/3), higher expression and phosphorylation of NMDA receptor (NRland NR2B) in hippocampus. Microinjection of WAY100635(the antagonist of5-HT1AR) into hippocampus resulted in similar animal depressive-like behaviors and the expression of kalirin-7, the expression and phosphorylation NMDA receptor and AMPA receptor with CUMS/SAL group. Pretreatment with microinjection of8-OH-DPAT (the agonist of5-HT1AR) could rescue such depression effect of CUMS, increase the expression of kalirin-7, the expressions of AMPA receptor (GluR2/3), and decrease the expressions of NMDA receptor (NR1and NR2B) in hippocampus.These results suggest that5-hydroxytryptamine (5-HT) may contribute to chronic stress induced depressive-like behaviors via5-HT1AR. The antidepressant effect of5-HT1A receptor agonists may be mediated by NMDA, AMPA receptor and kalirin-7. |
PDF Full Text Request