Abstract: Objective To investigate the effect of adenosine A1 receptor (A1R) agonist on learning and memory function of diabetic rats with depression. Methods The rats were divided into control group, model group and metformin(Met)group (0.18g/kg Metformin was given by ig. for 28 days) and metformin combined with adenosine A1 receptor agonist (Met+CPA) intervention group (metformin was given by ig, and then the CPA was intraperitoneally injected at 1 mg/kg from day 22 and administered for 7 days). The levels of blood glucose and learning/memory function in rats were observed. Then the concentration of glutamate in hippocampus was detected by ELISA. At last, the expression of GLT-1 and BDNF in hippocampus were detected by immunohistochemistry and Western-blot. Results Compared with the normal group, the content of blood glucose and the learning and memory function of the model group were significantly decreased(P<0.01). In addition, the concentration of glutamate in hippocampus was significantly increased(P<0.01), while the expression of GLT-1 and BDNF were significantly decreased(P<0.01或P<0.05). Compared with the model group, only the blood glucose level decreased significantly in Met group (P<0.01) with the other indexes did not change significantly. However, there was found that the levels of glucose in blood and glutamate in hippocampus were decreased significantly in Met + CPA group(P<0.01). Furthermore, the cognitive function was significantly improved and the expression of GLT-1 and BDNF were increased(P<0.01或P<0.05). Conclusion Activation of adenosine A1 receptor can effectively improve the cognitive function of diabetic rats with depression, which may be related to its anti-neurotoxicity by reducing the glutamate release and increasing neuronal nutrition function.

Key words: diabetes mellitus with depression, adenosine A1receptor, glial glutamate transporter-1, brain derived neurotrophic factor