曲唑酮对青春期雄性大鼠神经行为的影响及其相关机制研究

目的 探讨曲唑酮对青春期雄性大鼠神经行为的影响及其相关机制.方法 将32只SD大鼠按照随机数字表分为4组:曲唑酮低剂量组、中剂量组、高剂量组和对照组,分别给予10 mg/kg、20 mg/kg、50 mg/kg曲唑酮溶液腹腔注射,对照组腹腔注射等量生理盐水,连续注射14 d,结束后进行旷场实验、强迫游泳实验和水迷宫检测...

Effects of Trazodone on neurobehavior of adolescent male rats and its related mechanisms

Objective To investigate the effects of Trazodone on the neurobehavior of adolescent male rats and its related mechanisms.Methods 32 SD rats were randomly divided into 4 groups:Trazodone low-dose group,medium-dose group,high-dose group and control group,and they were intraperitoneally injected with Trazodone solution of 10 mg/kg,20 mg/kg and 50 mg/kg,respectively.The control group was intraperitoneally injected with the same amount of normal saline.All lasted for 14 consecutive days.Open field test,forced swimming test and water maze test were performed after the end.The expression and phosphorylation levels of ERK and P38 protein were detected by Western blot,and the expression of c-fos was detected by immunohistochemical staining.Results Compared with the control group and low-dose and high-dose groups,the total distance of exercise in open field box of rats(t₁=20.452,P₁<0.001;t₂=15.280,P₂<0.001;t₃=8.446,P₃<0.001)and center lattice residence time(t₁=11.971,P₁<0.001;t₂=10.658,P₂<0.001;t₃=14.963,P₃<0.001)in medium-dose group were significantly increased,and the low dose group was significantly higher than the control group(t₁=5.62,P₁<0.001;t₂=3.546,P₂=0.003),there was no significant difference between the two indexes in the high-dose group and the control group(P>0.05).Comparison of the number of rats entering the central grid among all groups showed statistically significant difference only between the control group and the medium-dose group,and the medium-dose group significantly increased compared with the control group(t=2.696,P=0.017),while there was no statistically significant difference among other groups(P>0.05).Compared with the other three groups,the immobility time in water was significantly reduced in the medium-dose group(t₁=3.017,P₁=0.009;t₂=2.8,P₂=0.013;t₃=2.523,P₃=0.03),and there was no significant difference among the three groups(P>0.05).Compared with the control group and the low-dose and high-dose groups,the stay time in the platform quadrant of rats in the medium-dose group(t₁=10.671,P₁<0.001;t₂=13.921,P₂<0.001;t₃=6.902,P₃<0.001)and crossing times(t₁=5.601,P₁<0.001;t₂=3.685,P₂=0.002;t₃=3.15,P₃=0.007)were significantly increased,while there was no significant difference between control group,low dose group and high dose group(P>0.05).Compared with control group and low-dose and high-dose groups,the proportion of c-fos expression in NeuN-labeled neurons of rats in medium-dose group was significantly decreased(t₁=2.483,P₁=0.042;t₂=3.781,P₂=0.007;t₃=2.388,P₃=0.048),while there was no significant difference between the control group,the low dose group and the high dose group(P>0.05).Compared with the control group and low-dose and high-dose groups,p-ERK/ERK in medium-dose group(t₁=3.332,P₁=0.013;t₂=2.476,P₂=0.042;t₃=2.886,P₃=0.023)and p-P38/P38 expression levels(t₁=4.378,P₁=0.003;t₂=9.148,P₂<0.001;t₃=3.385,P₃=0.012)were significantly decreased,while there was no significant difference between the control group,the low dose group and the high dose group(P>0.05).Conclusion Intraperitoneal injection of medium-dose Trazodone can relieve anxiety and depression and improve cognitive ability in rats.The mechanism may be related to the inhibition of MAPK signaling pathway by Trazodone and the decrease of 5-hydroxytryptamine(5-HT)and c-fos activity in neurons,of which the medium-dose Trazodone has the most significant effect.