| statistic difference between n-3 PUFA and clomipramine treated stress group and control group(P＞0.05).Sucrose intake and sucrose preference in both venlafaxine treated stress groups were higher than saline and olive oil treated stress groups (P＜0.05).There was no difference of body weight between drug-treated groups(P＞0.05).Conclusions(1)chronic mild stress could induce the depressive-live effect in rats.(2) N-3 polyunsaturated fatty acids could reverse the sucrose intake and sucrose preference reduction induced by CMS model.(3)Both dosage of venlafaxine could reverse the sucrose intake and sucrose preference reduction induced by CMS model. (4)N-3 polyunsaturated fatty acids have no effect on body weight. Objective The aim of the present study is to explore effect of n-3 polyunsaturated fatty acids on neurotransmission in the rats in chronic mild stress (CMS).Methods The whole experiment lasted for 8 weeks.Forty-three male Sprague-Dawley rats were used.All rats were divided into two groups randomly,the CMS group and control.After 4 weeks of stress,CMS group were subdivided into 5 groups:venlafaxine treated stress group(2.5mg·kg-1·d-1),olive oil treated stress group(0.72g·kg-1·d-1),fish oil treated stress group(0.72g·kg-1·d-1)and saline treated stress group(4mg·kg-1·d-1),and clomipramine(10mg·kg-1·d-1).4 weeks later,all rats were killed by decapitation next day.The 5-HT,DA and NE levels and their metabolic product in the hippocampus and frontal cortex were assayed using HPLC electrochemical detection.Results(1)Hippocampus①The concentration of 5-HT and 5-HIAA in fish oil treated stress group were lower than olive oil treated stress group(P＜0.05),and the level of DA was higher than olive oil treated stress group(P＜0.05).②The 5-HIAA level in clomipramine was lower than saline treated stress group(P＜0.05).③The 5-HIAA level in venlafaxine treated stress group was lower than olive oil treated stress group(P＜0.05).④There was no statistic difference of the MHPG and DOPAC between groups(P=0.772和P=0.461).(2)Frontal cortex①Compared with the control group,the level of 5-HT,5-HIAA,NE in olive oil treated stress group was higher(P＜0.05),DA was lower(P＜0.05).②The concentration of NE in saline group was higher than control(P＜0.05).③In clomipramine treated stress group, the level of 5-HT,5-HIAA,NE was lower,DA level was higher than olive oil treated stress group(P＜0.05);the level of 5-HT and NE was lower than that of saline treated stress group(P＜0.05).(4)In fish oil treated stress group,the level of 5-HT was lower,DA was higher than olive oil treated stress group(P＜0.05).⑤The level of 5-HT in venlafaxine treated stress group was lower than that of olive oil treated stress group(P＜0.05).⑥There was no statistic difference of the MHPG and DOPAC between groups. Conclusions(1)Chronic mild stress reinforces the function of 5-HT and NE, degrade the function of DA.(2)N-3 polyunsaturated fatty acids reverse the 5-HT and DA abnormality induced by CMS,and have no effect on the function of NE.(3) Venlafaxine reverses the 5-HT function induced by CMS,and have no effect on the function of NE and DA.(4)Clomipramine reverses the 5-HT,DA,and NE abnormality induced by CMS. Objective The aim of the present study is to explore the antidepressant-like effect of n-3 polyunsaturated fatty acids in gene expression in hippocampus in CMS rats.Methods The whole experiment lasted for 8 weeks.Twelve male Sprague-Dawley rats were subjected to the CMS for 4 weeks,then subdivided into 3 groups,which were administered with venlafaxine(2.5mg·kg-1·d-1)(3 rats),fish oil(0.72g·kg-1·d-1)(3 rats)and saline(4mg·mg·kg-1·d-1)(6 rats)for 4weeks. And then all rats were killed by decapitation next day.The hippocampus were carefully dissected and stored at -80℃.The total RNA was abstracted and then transcribed into cRNA.The cRNA were labeled with Cy5 and Cy3.The microarrays with more than 10,003 genes were hybridized against the cRNA probe mixture.The fluorescent signals were scanned.Results(1)n-3 polyunsaturated fatty acids regulated gene:①36 genes were regulated in fish oil treated stress groups when the ratio of Cy5/Cy3 signals was more than 2.0 or less than 0.5.Out of these 36 genes,12 genes were up-regulated and 23 down-regulated.②202 genes were regulated in fish oil treated stress groups when the ratio of Cy5/Cy3 signals was more than 1.67 or less than 0.67.Out of these 202 genes,71 genes were up-regulated and 131 down-regulated.Fish oil regulated genes included neuroimmune gene,signal pathway gene,neurotransmitter gene, neuropeptide related gene and others.(2)Venlafaxine regulated gene:①10 genes were up regulated in venlafaxine treated stress groups when the ratio of Cy5/Cy3 signals was more than 2.0 or less than 0.5.②80 genes were regulated in venlafaxine treated stress groups when the ratio of Cy5/Cy3 signals was more than 1.67 or less than 0.67.Out of these 80 genes,54 genes were up-regulated and 26 down-regulated. Venlafaxine regulated genes included drug transporter gene,ion channel gene, neurodevelopment gene,neural plasticity gene and other genes.(3)35 genes were co-regulated by n-3 polyunsaturated fatty acids and venlafaxine.①35 genes were regulated in venlafaxine treated stress groups when the ratio of Cy5/Cy3 signals was more than 1.67 or less than 0.67.Out of these 35 genes,16 genes were up-regulated and 19 down regulated.①No genes were regulated in venlafaxine treated stress groups when the ratio of Cy5/Cy3 signals was more than 1.67 or less than 0.67.N-3 polyunsaturated fatty acids and venlafaxine co-regulated gene include neuropeptide, neurotransmitter,GABA receptor,and mitochondria apoptosis,TNF related gene and other genes.Conclusions(1)The mechanism of antidepressant effect of N-3 polyunsaturated include the regulation of neuroimmune gene,signal pathway gene, neurotransmitter gene,neuropeptide related gene and other genes.(2)The mechanism of antidepressant effect of Venlafaxine includes the regulation of drug transporter gene,ion channel gene,neurodevelopment gene,neural plasticity gene and other genes.(3)N-3 polyunsaturated fatty acids and venlafaxine have co-regulated and solo-regulated genes,.
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