Effects of ceftriaxone on depressive-like behavior and changes of hippocampal glutamate transporter-1 in depression model C57 mice

Abstract

Objective To investigate the effects of ceftriaxone on depressive-like behavior and changes of hippocampal glutamate transporter-1(GLT-1) in C57 mice depression model, and to further explore the molecular mechanism of ceftriaxone on antidepressant action. Methods Thirty male C57 mice were randomly divided into control group(group A, n=10), CUS group(group B, n=10) and CUS+ ceftriaxone group(group C, n=10). The mice of the CUS group and the CUS+ ceftriaxone group were subjected to chronic unpredictable stress (CUS) for 2 sessions per day for 21 days. Then, the mice of the CUS+ ceftriaxone group were given ceftriaxone for 21 days. Behavioral changes were assessed by the sucrose preference test and open field test.The GLT-1 protein levels in the hippocampus were detected by Western blot analysis at the end of the ceftriaxone treatment. Results (1) Compared with the control group, the percentage of sucrose preference, the total traveled distance, the moved velocity, and the frequencies of rearing of the CUS group were significantly decreased(P<0.05) at the 21 days. However, the percentage of sucrose preference((78.74±3.54)%), the total traveled distance((6818.35±505.14)cm), the moved velocity((12.36±0.89)cm/s), and the frequencies of rearing(58.20±4.05) of the CUS+ ceftriaxone group at the end of the ceftriaxone treatment were improved significantly compared with the CUS group((59.46±2.75)%, (2931.71±271.89)cm, (5.84±0.42)cm/s, (26.20±2.62), P<0.05). (2) Western blot analysis indicated significant reductions of the GLT-1 protein levels in the hippocampus of CUS group (versus the control mice: P<0.05), and chronic ceftriaxone treatment reversed the CUS-induced decrease in the GLT-1 levels(P<0.05). Conclusion Ceftriaxone might significantly improve depressive-like behavior in C57 mice depression model. Chronic unpredictable stress (CUS) could down-regulate the GLT-1 protein levels in the hippocampus, which are reversed by ceftriaxone. These results further support the notion enhanced expression of the GLT-1 protein can be molecular mechanism of ceftriaxone on antidepressant action. Key words: Ceftriaxone; C57 mice; Chronic unpredictable stress; Glutamate transporter 1; Hippocampus; Depression