普萘洛尔联合记忆唤起再巩固范式干预酒精依赖患者酒精渴求的研究

Propranolol combined with memory retrieval reconsolidation procedure for the intervention of alcohol craving in patients with alcohol dependence

目的探索普萘洛尔联合记忆唤起再巩固范式对酒精依赖患者酒精渴求的影响。方法纳入符合DSM-Ⅳ中关于酒精依赖诊断标准的54例酒精依赖患者,采用随机数字表法将患者分为研究组(n=28)和对照组(n=26)。研究组采用普萘洛尔联合记忆唤起再巩固范式,对照组采用安慰剂联合记忆唤起再巩固范式。在基线、关联学习、记忆检测阶段采用可视渴求量表(Visual Analog Scale,VAS)评估对酒瓶、倒酒、饮酒等图片(酒精相关线索图片,既往线索)及中性图片(新线索)诱发的酒精渴求程度,采用收缩压、舒张压、心率水平评估线索反应性。重复测量方差分析比较2组渴求程度,收缩压、舒张压以及心率水平的差异,并对线索反应性指标与渴求程度进行相关性分析。结果关联学习阶段:与学习前相比,条件性刺激(conditioned stimulus)关联学习(简称CS+,即中性图片与酒精配对学习)后2组收缩压、舒张压、心率水平均有不同程度的升高(F=52.79、42.44、49.53,均P<0.05);与基线相比,2组关联学习中性图片诱发的渴求程度的VAS评分升高(F=99.88、68.69,均P<0.01)。记忆检测阶段:(1)与对照组酒瓶、倒酒、饮酒图片及中性图片诱发的渴求程度的VAS评分相比,研究组的VAS评分降低(F=7.38、13.27、11.34、4.62,均P<0.05)。与关联学习阶段酒瓶、倒酒、饮酒图片及中性图片诱发的渴求程度的VAS评分相比,记忆检测阶段研究组的VAS评分显著降低(F=43.89、23.53、15.93、31.01,均P<0.05),而对照组的倒酒、饮酒图片诱发的渴求程度VAS评分显著升高(F=13.40、63.65,均P<0.05)。(2)记忆检测后,与对照组相比,研究组舒张压、心率水平降低(F=20.99、15.42,均P<0.05);与检测前相比,检测后研究组舒张压、心率水平降低(F=4.11、8.05,均P<0.05),对照组舒张压、心率水平升高(F=81.86、41.13,均P<0.05)。(3)研究组记忆检测前后舒张压差值与记忆检测与关联学习的中性图片诱发的渴求程度的VAS评分差值呈正相关(r=0.394,P=0.038);记忆检测前后心率差值与记忆检测与关联学习的饮酒图片诱发的渴求程度的VAS评分差值呈正相关(r=0.389,P=0.041)。结论普萘洛尔联合记忆唤起再巩固范式可降低酒精依赖患者既往线索和新线索诱发的酒精渴求。

Objective This study aims to explore the effect of propranolol combined with memory retrieval reconsolidation procedure on alcohol craving.Methods A total of 54 patients with alcohol dependence who met the diagnostic criteria for alcohol dependence in DSM-Ⅳwere enrolled.The patients were randomly located into the alcohol retrieval-propranolol group(study group,n=28)and the alcohol retrieval-placebo group(control group,n=26)using the random number table.The study group used propranolol combined with a memory retrieval reconsolidation procedure,while the control group used a placebo combined with a memory retrieval reconsolidation procedure.The Visual Analog Scale(VAS)was used to evaluate the degree of alcohol craving induced by images such as wine bottle,pouring wine,and drinking(alcohol-related cue images,previous cue images)and neutral images(new cue)at stages of baseline measures,relevance learning,and memory test.The systolic blood pressure,diastolic blood pressure,and heart rate were applied to evaluate cue responsiveness.Repeated measures analysis of variance was used to compare the craving degree,systolic blood pressure,diastolic blood pressure,and heart rate between the two groups.The correlation between cue responsiveness and craving degree was analyzed.Results Relevance learning stage:Compared with before learning,the levels of systolic blood pressure,diastolic blood pressure,and heart rate of the two groups increased in varying degrees after learning conditional stimulation-relevance learning+(CS+,namely neutral images paired learning with alcohol)(F=52.79,42.44,49.53,P<0.05).Compared with the baseline measures,the VAS of neutral images in relevancy learning increased(F=99.88,68.69,both P<0.01).Memory test stage:(1)Compared with the control group,the VAS scores of cravings induced by wine bottles,pouring wine,drinking images,and neutral images were lower in the study group(F=7.38,13.27,11.34,4.62,P<0.05).Compared with the VAS scores of cravings induced by wine bottles,pouring wine,drinking images,and neutral images in the relevance learning stage,the VAS scores of the study group in the memory test stage were significantly lower(F=43.89,23.53,15.93,31.01,P<0.05).For the control group,VAS scores induced by pouring wine and drinking images were significantly increased(F=13.40,63.65,P<0.05).(2)After the memory test stage,compared with the control group,the levels of diastolic blood pressure and heart rate in the study group decreased(F=20.99,15.42,P<0.05).Compared with before the test,the levels of diastolic blood pressure and heart rate in the study group decreased after the test(F=4.11,8.05,P<0.05),while those in the control group increased(F=81.86,41.13,P<0.05).(3)The difference in diastolic blood pressure before and after the memory test stage was positively correlated with the difference in neutral VAS score between the memory test and association learning(r=0.394,P=0.038).Heart rate difference before and after the memory test stage positively correlated with the VAS score difference between the memory test and associated learning drinking images(r=0.389,P=0.041).Conclusion Propranolol combined with memory retrieval reconsolidation procedure can reduce alcohol cravings induced by previous and new cues in patients with alcohol dependence.