Effect of inhibition of reactivated alcohol-associated memories with propranolol on alcohol craving.

Abstract

Background: Alcohol craving and relapse occur after the reactivation of alcohol reward memory. Previous studies suggest that drug-associated memory undergoes reconsolidation once retrieved by drug-associated stimuli. This study hypothesized that propranolol administration during memory reconsolidation induced by conditioned stimulus (CS) would significantly attenuate alcohol craving.

Methods: A total of 40 patients with alcohol dependence who met the diagnostic criteria for alcohol dependence in DSMV were enrolled. The patients were randomized located into the memory retrievalpropranolol group (n = 20) and the memory retrievalplacebo group (n = 20) using the random number table. The memory retrievalpropranolol group used propranolol combined with a memory retrieval reconsolidation procedure, while the memory retrievalplacebo 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 at stages of baseline measures, relevance learning, and memory test. The systolic blood pressure, diastolic blood pressure, and heartrate were applied to evaluate cue responsiveness. Repeated measures analysis of variance was used to compare the craving degree and independent samples t-tests were used for comparing demographic characteristics, scale scores between alcohol-dependent patient groups, and pre-post differences in heart rate, systolic blood pressure, and diastolic blood pressure at each experimental phase.

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 stimulationrelevance learning CS+(all P < 0.05). Compared with pre-learning, both groups showed increased VAS scores during the Retrieval phase with statistically significant differences (F = 47.294、25.015, all P < 0.001). The memory test stage, after re-exposure to learned CS+, both groups showed varying degrees of increase in heart rate, systolic blood pressure, and diastolic blood pressure, with all differences reaching statistical significance (all P < 0.05). During the test phase, statistically significant between-group differences were found in heart rate difference, systolic blood pressure difference and diastolic blood pressure difference between the two groups (all P < 0.05). the retrieval-propranolol group demonstrated decreased VAS scores with statistical significance (F = 56.017, P < 0.001), while the retrieval-placebo group showed no statistically significant alterations in VAS scores (F = 0.183, P > 0.05).

Conclusions: Our study demonstrated that propranolol administration after CS-induced retrieval could disrupt alcohol-associated memory reconsolidation and reduce alcohol craving. The finding provided a potential translational method to treat alcohol use disorder.

Trial registration: The protocol was registered at www.chictr.org.cn on October 13, 2023 (Chinese Clinical Trial Registry, identification number ChiCTR2300076633, Retrospectively registered).