Effects Of β-Blocker On Memory Reconsolidation Of Alcohol Reward Evoked By Unconditioned Stimulation

BackgroundAlcohol dependence is a chronic recurrent encephalopathy.The long-term existence of reward memory associated with alcohol-related conditional cues is the root cause of craving and redrinking,so interfering with reward memory is the key to the treatment of alcohol dependence.Some studies have shown that interfering with the reconsolidation process of conditioned stimulus evoking reward memory can eliminate the reward memory associated with conditioned stimulus,but it can not eliminate the reward memory that is not associated with the conditioned stimulus.However,alcohol dependent patients often form reward memories related to multiple conditional cues.Exposure to these conditional cues can evoke alcohol reward memories,cause craving,and lead to redrinking.In order to completely eliminate the reward memory of alcohol,unconditioned stimulation was used to evoke the reward memory of patients with alcohol dependence,and propranolol was given to interfere with the re-consolidation process of reward memory,in order to completely eliminate the reward memory of alcohol,reduce craving and reduce redrinking.ObjectivesTo explore the effect of β-blocker on the reconsolidation of alcohol reward memory evoked by unconditioned stimulation,so as to provide new ideas and scientific basis for clinical treatment of alcohol dependence.Methods1.Research objects and groups Eighty-one patients with alcohol dependence who met the admission criteria in the Department of Addiction Medicine,the second affiliated Hospital of Xinxiang Medical College from October 2019 to December 2020 were randomly divided into three groups: A.Alcohol arousal-propranolol group;B.Alcohol arousal-placebo group;C.Alcohol arousal-6 hours-propranolol group.General demogra Phic data were collected and scales were evaluated.2.General demographic data were collected and scales were evaluated.3.Experimental design The design of this study was divided into four stages,namely,general data collection stage,association learning stage(CS+,CS-),memory arousal and re-consolidation intervention stage and testing stage.All alcohol dependent patients were exposed to alcohol bottles,pouring alcohol,drinking and other environments(old memories related to alcohol)and alcohol-related learning with neutral pictures(circle or triangle)(new learning memory)and alcohol-related learning.After evoking reward memory with unconditioned stimulation,placebo 20 mg or propranolol 20 mg was given immediately or propranolol 20 mg 6 hours later.Heart rate and blood pressure were monitored during association learning,arousal and testing.Visual analogue score was used to assess alcohol craving(alcohol-related old memory)and preference(new learning memory)to evaluate reward memory.4.Statistical method Statistical software SPSS22.0 was used for statistical analysis,and P < 0.05 was considered to be statistically significant.Results1.There was no significant difference in the scores of general demographic data and scales in patients with alcohol dependence(P > 0.05).2.Relevance learning stage(CS+,CS-)The systolic blood pressure(SBP),diastolic blood pressure(DBP)and heart rate(HR)of the three groups increased in different degrees after association learning CS+,but there was no significant difference among the three groups before and after association learning(P > 0.05).The systolic blood pressure(SBP),diastolic blood pressure(DBP)and heart rate(HR)of the three groups were significantly higher than those of the three groups before and after association learning(P > 0.05).When learning CS-,there was no significant difference in systolic blood pressure,diastolic blood pressure and heart rate among the three groups before and after association learning(P > 0.05),and there was no significant difference in systolic blood pressure,diastolic blood pressure and heart rate among the three groups before and after association learning(P > 0.05).3.The intervention stage of memory arousal and re-consolidation After arousal,compared with before arousal,the systolic blood pressure,diastolic blood pressure and heart rate in the three groups increased in varying degrees,and the difference was statistically significant(P < 0.05).There was no significant difference in systolic blood pressure,diastolic blood pressure and heart rate between the three groups before and after arousal(P > 0.05).4.Detection stage(1)Detection of systolic blood pressure,diastolic blood pressure and heart rate After detection,the systolic blood pressure,diastolic blood pressure and heart rate in alcohol arousal-propranolol group decreased in varying degrees,and the difference was statistically significant(P < 0.05).However,the systolic blood pressure,diastolic blood pressure and heart rate in alcohol arousal-placebo group and alcohol arousal-6 h-propranolol group increased,and the difference was statistically significant(P < 0.05).(2)Craving and preference for testing After the test,the "preference" and "craving" of the alcohol-arousing propranolol group decreased to different degrees compared with before the test,with statistical significance(P < 0.05).However,the degree of "craving" and "preference" in alcohol arousal-placebo group and alcohol arousal-6 hours-propranolol group were increased,with statistical significance(P < 0.05).Conclusions1.Intervention with propranolol within the reconsolidation time window after unconditioned stimulation arousing reward memory can reduce craving for alcohol in alcohol-dependent patients.2.Intervention with propranolol within the reconsolidation window after reward memory arousal as opposed to placebo interfered with the reconsolidation process and affected alcohol-related cravings.Replacement of propranolol beyond 6 hours after the reconsolidation window did not affect alcohol-related cravings.3.Unconditioned stimulation evokes reward memories,and propranolol intervention during the reconsolidation window erases both newly and preexisting memories and alcohol-related memories.