Objective　To observe the growth-associated protein-43(GAP-43),synaptophysin (SYN) and postsynaptic density 95（PSD95） in the amygdala of rats with epilepsy-associated depression (EAD),and to explore the role of these three synaptic-related proteins in the pathogenesis of EAD.Methods　Healthy adult SD rats were randomly divided into comorbidity group,epilepsy group,depression group and normal group.The lithium chloride-pilocarpine method was used to establish the epilepsy model.The epilepsy model was screened for depression 14 days after the model was established.The rats with epilepsy and depression were the comorbid group;the rats without depression were the epilepsy group.The chronic depression model was established in the depression group by chronic unpredictable moderate stress stimulation combined with orphan method.The normal group is healthy SD rats.On the 29th day (4 weeks later) after the successful modeling,the brain was taken out by intravital perfusion and fixation in vivo,and the amygdala was separated from the brain tissue.The immunohistochemical staining was used to detect the expression of GAP43,PSD95 and SYN protein in the amygdala of rats in each group.Results　Compared with the control groups,the number of GAP-43 and PSD95 immunohistochemical positive cells in the comorbid group was the least,and the normal control group was the most (P<0.05).There was no statistical significance in the other groups (P>0.05).Compared with the epilepsy group and the normal group,the SYN immunohistochemical positive cell expression in the comorbid group and depression group was reduced (P<0.05).The epilepsy group was more than that of the depression group,and less than that of the normal group (P<0.05).Conclusion　The decreased expression of GAP-43,SYN,and PSD95 in the amygdala of epileptic rats with depression may be related to the onset of depression in epilepsy rats.