7,8-二羟基黄酮对间歇性主动饮酒模型大鼠饮酒量的影响
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摘要
目的研究7,8-DHF对间歇性主动饮酒大鼠饮酒量的影响。方法将24只雄性SD大鼠随机分为对照组(n=6)和模型组(n=18,间歇性主动饮酒28天),其中模型组分为模型对照组(n=6),7,8-DHF组(n=6,一次性腹腔注射5mg/kg的7,8-DHF),DMSO组(n=6,一次性腹腔注射等量的DMSO)、观察大鼠饮酒量的变化。结果模型组与对照组比较体重无差别,模型组间歇性主动饮酒28天,饮酒量及酒精偏好达到稳定状态,成功建立酒精依赖模型。与模型对照组比较,7,8-DHF组饮酒量显著降低(P<0.05)。与模型对照组比较,7,8-DHF组大鼠酒精偏好明显减低,具有统计学差异(P<0.01)。结论大鼠间歇性主动饮酒28天成功建立酒精依赖模型,7,8-DHF显著降低间歇性主动饮酒大鼠的饮酒量。
Objective To study the effect of 7,8-DHF on alcohol consumption in rats with intermittent active drinking. Methods Twenty-four male Sprague-Dawley rats were randomly divided into control group( n = 6) and model group( n = 18) for intermittent active drinking for 28 days. The model group was further divided into model control group( n = 6),DMSO group( n = 6),and 7,8-DHF group( n = 6) which was given a one-time intraperitoneal injection of 7,8-DHF( 5 mg/kg). The changes in the amount of alcohol consumed in the rats were observed. Results There was no difference in body weight between the model group and the control group. After 28 days of intermittent active drinking in the model group,the alcohol consumption and alcohol preference reached a steady state,and the alcohol dependence model was successfully established. Compared with the model control group,the alcohol consumption in the 7,8-DHF group was significantly lower( P<0.05); Compared with the model control group,the alcohol preference of the rats in the 7,8-DHF group was significantly lower( P<0.01).The difference was statistically significant.Conclusion Intermittent active drinking for 28 days successfully established a rat alcohol dependence model,and 7,8-DHF could significantly reduce the alcohol consumption of intermittent active drinking rats.
Objective To study the effect of 7,8-DHF on alcohol consumption in rats with intermittent active drinking. Methods Twenty-four male Sprague-Dawley rats were randomly divided into control group( n = 6) and model group( n = 18) for intermittent active drinking for 28 days. The model group was further divided into model control group( n = 6),DMSO group( n = 6),and 7,8-DHF group( n = 6) which was given a one-time intraperitoneal injection of 7,8-DHF( 5 mg/kg). The changes in the amount of alcohol consumed in the rats were observed. Results There was no difference in body weight between the model group and the control group. After 28 days of intermittent active drinking in the model group,the alcohol consumption and alcohol preference reached a steady state,and the alcohol dependence model was successfully established. Compared with the model control group,the alcohol consumption in the 7,8-DHF group was significantly lower( P<0.05); Compared with the model control group,the alcohol preference of the rats in the 7,8-DHF group was significantly lower( P<0.01).The difference was statistically significant.Conclusion Intermittent active drinking for 28 days successfully established a rat alcohol dependence model,and 7,8-DHF could significantly reduce the alcohol consumption of intermittent active drinking rats.
引文
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[16]BRIONES T L,WOODS J.Chronic binge-like alcohol consumption in adolescence causes depression-like symptoms possibly mediated by the effects of BDNF on neurogenesis[J].Neuroscience,2013(254):324-334.
[17]HAUSER S R,GETACHEW B,TAYLOR R E,et al.Alcohol induced depressive-like behavior is associated with a reduction in hippocampal BDNF[J].Pharmacol Biochem Behav,2011,100(2):253-258.
[2]KAPOOR.Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism[J].Translational Psychiatry,2019,9(1):89.
[3]ORGANIZATION W H.Global status report on alcohol and health2014[J].Global Status Report on Alcohol,2014,18(7):1-57.
[4]PARDON M C.Role of neurotrophic factors in behavioral processes:implications for the treatment of psychiatric and neurodegenerative disorders[J].Vitam Hom,2010,82(82):185-200.
[5]SUSICK L L,CHRUMKA A C,HOOL S M,et al.Dysregulation of TrkB phosphorylation and pro BDNF protein in adenylyl cyclase 1and 8 knockout mice in a model of fetal alcohol spectrum disorder[J].Alcohol,2016,51:25-35.
[6]LIU C,CHAN C B,YE K.7,8-dihydroxyflavone,a small molecular Trk B agonist,is useful for treating various BDNF-implicated human disorders[J].Translational Neurodegeneration,2016,5(1):2-9.
[7]JANG S W,LIU X,YEPES M,et al.A selective Trk B agonist with potent neurotrophic activities by 7,8-dihydroxyflavone[J].Proceedings of the National Academy of Sciences,2010,107(6):2687-2692.
[8]CASTELLO N A,NGUYEN M H,TRAN J D,et al.7,8-Dihydroxyflavone,a Small Molecule TrkB Agonist,Improves Spatial Memory and Increases Thin Spine Density in a Mouse Model of Alzheimer Disease-Like Neuronal Loss[J].Plos One,2014,9(3):e91453.
[9]CHAO Y L,CHI B C,AND K Y.7,8-dihydroxyflavone,a Trk B receptor agonist,blocks long-term spatial memory impairment caused by immobilization stress in rats[J].Hippocampus,2012,22(3):399-408.
[10]ZHANG Z,LIU X,SCHROEDER J P,et al.7,8-Dihydroxyflavone Prevents Synaptic Loss and Memory Deficits in a Mouse Model of Alzheimer’s Disease[J].Neuropsychopharmacology,2014,39(3):638-650.
[11]LI J,CHENG Y,BIAN W,et al.Region-specific Induction of Fos B/os B by Voluntary Alcohol Intake:Effects of Naltrexone[J].Alcoholism Clinical Experimental Research,2010,34(10):1742-1750.
[12]CARNICELLA S,AMAMOTO R,RON D.Excessive alcohol consumption is blocked by glial cell line-derived neurotrophic factor[J].Alcohol,2009,43(1):35-43.
[13]MARIAN L L,SEGEV B,VINCENT W.Corticostriatal BDNF and alcohol addiction[J].Brain Research,2015,1628(Pt A):60-67.
[14]HUANG M C,CHEN C H,LIU H C,et al.Differential Patterns of Serum Brain-Derived Neurotrophic Factor Levels in Alcoholic Patients With and Without Delirium Tremens During Acute Withdrawal[J].Alcoholism Clinical&Experimental Research,2011,35(1):126-131.
[15]NIKOLAKOPOULOU A M,MEYNARD M M,MARSHAK S,et al.Synaptic maturation of the Xenopus retinotectal system:Effects of brain-derived neurotrophic factor on synapse ultrastructure[J].Journal of Comparative Neurology,2010,518(7):972-989.
[16]BRIONES T L,WOODS J.Chronic binge-like alcohol consumption in adolescence causes depression-like symptoms possibly mediated by the effects of BDNF on neurogenesis[J].Neuroscience,2013(254):324-334.
[17]HAUSER S R,GETACHEW B,TAYLOR R E,et al.Alcohol induced depressive-like behavior is associated with a reduction in hippocampal BDNF[J].Pharmacol Biochem Behav,2011,100(2):253-258.