基于不同年龄阶段大鼠对慢性温和不可预知应激模型的优化
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摘要
目的比较不同年龄阶段大鼠对慢性温和不可预知应激(unpredictable chronic mild stress,UCMS)模型的敏感程度。方法将幼年(3周龄)及成年(8周龄)的雄性SD大鼠经过糖水基线筛选和剔除后分组,分别随机分为对照组和实验组(UCSM组),每组8只。随后对UCMS组进行连续5周的慢性温和不可预知应激。按随机化方法对各应激处理排表,避免大鼠预料其出现而适应。在应激后第1,3,5周分别对所有大鼠进行糖水偏好实验和强迫游泳实验。结果幼年大鼠接受应激1周后在糖水偏好实验中表现出快感缺乏行为(t=2. 192,P=0. 046),应激3周后在强迫游泳实验中表现出抑郁样行为(t=3. 464,P=0. 006);成年大鼠在接受应激5周时出现类似快感缺乏行为(t=3. 587,P=0. 003)及抑郁样行为(t=2. 207,P=0. 045)。幼年UCMS组糖水偏好指数平均值显著低于幼年对照组、成年对照组和成年UCMS组(F=19. 927,P <0. 001);而不动时间显著高于其他三组(F=19. 663,P <0. 001)。结论幼年期暴露于UCMS的大鼠行为学改变的敏感性和反应强度均高于成年期大鼠。
Objective To optimize the unpredictable chronic mild stress( UCMS) model based on the different ages of rats. Methods Juvenile( three weeks old) and adult( eight weeks old) male SD rats were divided into control group and UCMS group randomly( n =8 for each group) according to the screening by the baseline of sucrose preference test. The rats in UCMS group were subjected to chronic mild and unpredictable stress for five weeks. Randomized stressors were arranged to avoid the adaptation of the rats. The sucrose preference test and forced swimming test were conducted at the end of 1,3 and 5 weeks of UCMS. Results The juvenile rats showed anhedonia behavior in sucrose preference test after one week of UCMS( t = 2. 192,P = 0. 046) and depression-like behavior in forced swimming test after 3 weeks of UCMS( t = 3. 464,P = 0. 006). The adult rats showed the similar anhedonia behaviors( t = 3. 587,P =0. 003) and depression-like behavior after five weeks of UCMS( t = 2. 207,P = 0. 045). The average sucrose consumption of juvenile rats in UCMS group was significantly lower than that of juvenile rats in control group,adult rats in UCMS group and adult rats in control group( F = 19. 927,P < 0. 001). The immobility time of juvenile rats in UCMS group was significantly longer than that of the other three groups( F = 19. 663,P < 0. 001). Conclusion Compared with adult rats,juvenile rats exposed to UCMS show more sensitive and susceptible in behavioral tests.
Objective To optimize the unpredictable chronic mild stress( UCMS) model based on the different ages of rats. Methods Juvenile( three weeks old) and adult( eight weeks old) male SD rats were divided into control group and UCMS group randomly( n =8 for each group) according to the screening by the baseline of sucrose preference test. The rats in UCMS group were subjected to chronic mild and unpredictable stress for five weeks. Randomized stressors were arranged to avoid the adaptation of the rats. The sucrose preference test and forced swimming test were conducted at the end of 1,3 and 5 weeks of UCMS. Results The juvenile rats showed anhedonia behavior in sucrose preference test after one week of UCMS( t = 2. 192,P = 0. 046) and depression-like behavior in forced swimming test after 3 weeks of UCMS( t = 3. 464,P = 0. 006). The adult rats showed the similar anhedonia behaviors( t = 3. 587,P =0. 003) and depression-like behavior after five weeks of UCMS( t = 2. 207,P = 0. 045). The average sucrose consumption of juvenile rats in UCMS group was significantly lower than that of juvenile rats in control group,adult rats in UCMS group and adult rats in control group( F = 19. 927,P < 0. 001). The immobility time of juvenile rats in UCMS group was significantly longer than that of the other three groups( F = 19. 663,P < 0. 001). Conclusion Compared with adult rats,juvenile rats exposed to UCMS show more sensitive and susceptible in behavioral tests.
引文
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[11]Liu J,Zhu HX,Fu WL,et al.Downregulated hippocampal expression of brain derived neurotrophic factor and tyrosine kinase Bin a rat model of comorbid epilepsy and depression[J].Neurol Res,2019,41(5):437-445.
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[14]Bogdanova OV,Kanekar S,D'Anci KE,et al.Factors influencing behavior in the forced swim test[J].Physiol Behav,2013,118:227-239.
[15]肖玲.不同时程慢性应激对大鼠抑郁行为与海马神经可塑性相关蛋白BDNF/CREB/Bcl-2的影响[D].武汉:武汉大学,2013.
[16]Spangler E,Cote DM,Anacker AM,et al.Differential sensitivity of the perioculomotor urocortin-containing neurons to ethanol,psychostimulants and stress in mice and rats[J].Neuroscience,2009,160(1):115-125.
[17]Xing Y,He J,Hou J,et al.Gender differences in CMS and the effects of antidepressant venlafaxine in rats[J].Neurochem Int,2013,63(6):570-575.
[18]Teicher MH,Samson JA.Annual research review:enduring neurobiological effects of childhood abuse and neglect[J].J Child Psychol Psychiatry,2016,57(3):241-266.
[2]Willner P,Muscat R,Papp M.Chronic mild stress-induced anhedonia:a realistic animal model of depression[J].Neurosci Biobehav Rev,1992,16(4):525-534.
[3]Willner P.Chronic mild stress(CMS)revisited:consistency and behavioural-neurobiological concordance in the effects of CMS[J].Neuropsychobiology,2005,52(2):90-110.
[4]Boufleur N,Antoniazzi CT,Pase CS,et al.Neonatal handling prevents anxiety-like symptoms in rats exposed to chronic mild stress:behavioral and oxidative parameters[J].Stress,2013,16(3):321-330.
[5]Dubey VK,Ansari F,Vohora D,et al.Possible involvement of corticosterone and serotonin in antidepressant and antianxiety effects of chromium picolinate in chronic unpredictable mild stress induced depression and anxiety in rats[J].J Trace Elem Med Biol,2015,29:222-226.
[6]Willner P.Validity,reliability and utility of the chronic mild stress model of depression:a 10-year review and evaluation[J].Psychopharmacology(Berl),1997,134(4):319-329.
[7]Ma XC,Jiang D,Jiang WH,et al.Social isolation-induced aggression potentiates anxiety and depressive-like behavior in male mice subjected to unpredictable chronic mild stress[J].PLo SOne,2011,6(6):e20955.
[8]Dvir Y,Ford JD,Hill M,et al.Childhood maltreatment,emotional dysregulation,and psychiatric comorbidities[J].Harv Rev Psychiatry,2014,22(3):149-161.
[9]Aya-Ramos L,Contreras-Vargas C,Rico JL,et al.Early maternal separation induces preference for sucrose and aspartame associated with increased blood glucose and hyperactivity[J].Food Funct,2017,8(7):2592-2600.
[10]Gross M,Pinhasov A.Chronic mild stress in submissive mice:Marked polydipsia and social avoidance without hedonic deficit in the sucrose preference test[J].Behav Brain Res,2016,298(Pt B):25-34.
[11]Liu J,Zhu HX,Fu WL,et al.Downregulated hippocampal expression of brain derived neurotrophic factor and tyrosine kinase Bin a rat model of comorbid epilepsy and depression[J].Neurol Res,2019,41(5):437-445.
[12]Slattery DA,Cryan JF.Using the rat forced swim test to assess antidepressant-like activity in rodents[J].Nat Protoc,2012,7(6):1009-1014.
[13]Yankelevitch-Yahav R,Franko M,Huly A,et al.The forced swim test as a model of depressive-like behavior[J].J Vis Exp,2015,(97):doi:10.3791/52587.
[14]Bogdanova OV,Kanekar S,D'Anci KE,et al.Factors influencing behavior in the forced swim test[J].Physiol Behav,2013,118:227-239.
[15]肖玲.不同时程慢性应激对大鼠抑郁行为与海马神经可塑性相关蛋白BDNF/CREB/Bcl-2的影响[D].武汉:武汉大学,2013.
[16]Spangler E,Cote DM,Anacker AM,et al.Differential sensitivity of the perioculomotor urocortin-containing neurons to ethanol,psychostimulants and stress in mice and rats[J].Neuroscience,2009,160(1):115-125.
[17]Xing Y,He J,Hou J,et al.Gender differences in CMS and the effects of antidepressant venlafaxine in rats[J].Neurochem Int,2013,63(6):570-575.
[18]Teicher MH,Samson JA.Annual research review:enduring neurobiological effects of childhood abuse and neglect[J].J Child Psychol Psychiatry,2016,57(3):241-266.