Effects of fluoxetine and escitalopram on depressive-like behavior and hippocampal BDNF gene expression in adult rats

Abstract

Objective To investigate the effects of different duration of fluoxetine and escitalopram administration on depressive-like behavior and hippocampal BDNF expression in adult rats. Methods Ninety-six SD rats were randomly divided into twelve groups: (1)M1 group: normal control for one week, (2)M2 group: CUMS+ saline for one week, (3)M3 group: CUMS+ fluoxetine for one week, (4) M4 group: CUMS+ escitalopram for one week, (5)M5 group: normal control for two weeks, (6)M6 group: CUMS+ saline for two weeks, (7)M7 group: CUMS+ fluoxetine for two weeks, (8)M8 group: CUMS+ escitalopram for two weeks, (9)M9 group: normal control for three weeks, (10)M10 group: CUMS+ saline for three weeks, (11)M11 group: CUMS+ fluoxetine for three weeks, (12) M8 group: CUMS+ escitalopram for three weeks. After CUMS procedures, rats in M2 group, M6 group and M10 group were injected with saline, M3 group, M7 group and M11 group were injected with fluoxetine, and rats in M4 group, M8 group, M12 group were injected with escitalopram. After one week of intervention, the open-field test and 1% sucrose preference test were performed to evaluate depression-like behaviors in rats of M1 group, M2 group, M3 group and M4 group. After behavior test, rats were sacrificed and the hippocampi were isolated. The expression of BDNFmRNA was detected by using real-time quantitative PCR. After two weeks of intervention, rats in M5 group, M6 group, M7 group and M8 group underwent the same behavioral. After three weeks of intervention, rats in M9 group, M10 group, M11 group and M12 group underwent the same behavioral test. Results In the open-field test, total distance travelled in 10 minutes was significant difference among the following groups: M1 group ((3925.70±322.32) cm) vs M3 group ((1841.85±786.33) cm), M6 group ((1820.31±296.00) cm) vs M8 group ((4002.72±1447.19) cm), M10 ((1961.66±919.16) cm) group vs M11 group ((3741.72±1064.46 ) cm), M10 group ((1961.66±919.16) cm) vs M12 group ((4280.43±1187.05) cm). In the 1% sucrose preference test, the difference of sucrose preference consumption was statistically significant (P<0.05) among the following groups: M2 group ((56.23±7.49)%) vs M4 group ((70.55±4.96)%), M6 group ((60.22±8.81)%) vs M8 group ((75.08±4.15)%), M10 group ((60.26±7.20)%) vs M11 group ((73.88±7.73)%), M10 group ((60.26±7.20)%) vs M12 group ((73.52±7.58)%). The expression level of BDNF was significant difference among these groups: M2 group (0.66±0.14) vs M4 group (1.15±0.20), M10 group (0.90±0.15) vs M11 group (1.22±0.09), M10 group (0.90±0.15) vs M12 group (1.48±0.20). Conclusion Both of fluoxetine and escitalopram can improve depression-like behaviors in rats and significantly increase the expression of the hippocampal BDNFmRNA. Compared with fluoxetine, escitalopram has a shorter onset time in the treatment of depression.It may be related with a rapid increase of the expression of BDNF mRNA. Key words: Fluoxetine; Escitalopram; Depression; Cyclic adenosine monophosphate response element binding protein; Brain derived neurotrophic factor