Effects Of Glutamic Acid On Spontaneous Discharges Of Arcuate Nucleus In Hypothalamic Slice From Normal And Inflamed Rats

To study the influence of glutamic acid (Glu) on the electric activities of hypothalamic arcuate nucleus (ARC) neurons in the normal rats and inflamed rats which were induced by complete Freund's adjuvant (CFA). The experiment was performed on isolated mediobasal hypothalamus slice to observe the effect of Glu on unit discharges of ARC neurons. The NMDA receptor agonist NMDA and NMDA receptor antagonist MK-801 were used to analyze the receptor mechanism of effect. The unit discharges were recorded extracellularly. The immunohistochemistry was imployed to observe the expression of NMDAR1 in the ARC neurons of normal rats and the CFA-inflamed rats.The experimental results indicated that: (1) Three types of spontaneous discharge (regular firing, irregular firing, firing in bursts) were observed in ARC neurons. (2) Glu can enhance the electric activities of ARC neurons. These effects can be mimicked by NMDA and blocked by MK-801. (3) The spontaneous discharge frequency of ARC neurons in CFA rats was higher than those in normal rats. (4) The excitatory effects of Glu and NMDA on the ARC neurons of CFA rats were more intensive. The spontaneous discharge frequency of ARC neurons increased significantly, the latency of drug action was shortened and the duration was lengthened. The excitatory response of ARC neurons to Glu and NMDA couldn't be blocked by CNQX ( the antagonist of non-NMDA glutamate receptor) but could be partly blocked by MK-801. (5) The results of immunohistochemistry indicated an up-regulation of the expression of NMDAR1 in the ARC neurons of the CFA rats.The results suggested that glutamate mechanism (mediated by NMDA receptor) is involved in the modulation of the electric activities of ARC neurons. The response of ARC neurons to glutamic acid is sensitized in CFA-inflamed rats.