The Essential Role Of Protein Kinase C In Morphological And Functional Changes Of Prelimbic Cortical Glutamatergic Synapse In Anxiety

Anxiety is one of the most prevalent mood disorders, in which the deficits of glutamatergic, serotonin and GABAergic synaptic functions in the amygdala and prefrontal cortex are presumably involved. But it is still unclear the pathological changes of the neural networks and excitatory synapses in these areas, as well as the underlying machenisms still remain elusive.A long-time belief is that the deficits of serotonergic and GABAergic synaptic transmission are associated with anxiety. Selective serotonin reuptake inhibitors and GABA receptor enhancers are used to treat anxiety disorders.Their effectiveness needs to be reevaluated due to unfavorable side effects. Recent reports show that glutamate is associated with anxiety and the antagonists of ionotropic glutamate receptor (iGluR) are potential reagents for anxiety therapy. In this regard, iGluR agonists hypothetically induce anxiety-related behavior. Here, we investigate roles and mechamism of the onotropic glutamatergic receptors in anxiety pathology. This study should provide a new target for treatment of anxiety.We investigated the anxiogenic role of the ionotropic glutamatergic receptor agonist kainic acid (KA). Further more, KA could induce the functional and mophological changes of excitatory synapses in prelimbic cortex. Blocking the activity of PKC by using the selective PKC antagonist chelerythrine chloride (CHE) reversed this kainate-induced anxiety as well as these anxiety-associated glutamatergic synapse changes in the prelimbic cortex. Our results indicated that KA, the ionotropic glutamatergic receptor agonist, played an important role in anxiety pathology, and PKC was essential for these changes. Also, we provided a protential therapic strategy for anxiety disorder.