Abstract
Environmental cues associated with drug abuse are powerful mediators of drug craving and relapse in substance-abuse disorders. Consequently, attenuating the strength of cue-drug memories could reduce the number of factors that cause drug craving and relapse. Interestingly, impairing cue-drug memory reconsolidation is a generally accepted strategy aimed at reducing the intensity of cues that trigger drug-seeking and drug-taking behaviors. In addition, the agranular insular cortex (AI) is an important component of the neural circuits underlying drug-related memory reconsolidation. GABAB receptors (GABABRs) are potential targets for the treatment of addiction, and baclofen (BLF) is the only prototypical GABAB agonist available for application in clinical addiction treatment. Furthermore, ΔFosB is considered a biomarker for the evaluation of potential therapeutic interventions for addiction. Here, we used the morphine-induced conditioned place preference (CPP) paradigm to investigate whether postretrieval microinjections of BLF into the AI could affect reconsolidation of drug-reward memory, reinstatement of CPP, and the level of ΔFosB in mice. Our results showed that BLF infused into the AI immediately following morphine CPP memory retrieval, but not 6 h postretrieval or following nonretrieval, could eliminate the expression of a morphine CPP memory. This effect persisted in a morphine-priming–induced reinstatement test, suggesting that BLF in the AI was capable of preventing the reconsolidation of the morphine CPP memory. Our results also showed that the elimination of morphine CPP memory was associated with reduced morphine-associated ΔFosB expression in the longer term. Taken together, the results of our research provide evidence to support that GABABRs in the AI have an important role in drug-cue memory reconsolidation and further our understanding of the role of the AI in drug-related learning and memory.
Highlights
Drug addiction is a serious public health concern worldwide and a chronic brain disorder molded by strong biosocial factors, leading to devastating consequences for individuals, families, and society (Volkow and Boyle, 2018; Padmanathan et al, 2019)
To address the above scientific questions in our study, we examined the effect of intra-agranular insular cortex (AI) infusions of the GABAB receptors (GABABRs) agonist, BLF, on the reconsolidation of drug reward memory using the conditioned place preference (CPP) paradigm, and the resulting memory alteration would be indicated by subsequent reduction in the time spent in the morphine-paired chamber
We could see that the expression of cFos in the insular cortex (IC) significantly increased in the retrieval group (F(2, 14) = 29.28, p < 0 .001, one-way ANOVA followed by Tukey's multiple comparison test, Figures 2C, D)
Summary
Drug addiction is a serious public health concern worldwide and a chronic brain disorder molded by strong biosocial factors, leading to devastating consequences for individuals, families, and society (Volkow and Boyle, 2018; Padmanathan et al, 2019). There is currently no effective treatment for drug addiction (YY et al, 2019), especially relapses following abstinence, and drug cravings are often triggered by environmental cues that are repeatedly paired with the psychotropic drug (Torregrossa and Taylor, 2013). Attenuating the strength of cue-drug memories could reduce the number of factors that cause drug craving and relapse, which can help to treat drug addiction (Torregrossa and Taylor, 2013). Recent studies have shown that pharmacological interventions following the retrieval of drug-related cues could disrupt the reconsolidation of drug memories, inhibit conditioned place preference (CPP), and inhibit operant drug craving and relapse after withdrawal (Sanchez et al, 2010; Hasbi et al, 2017). Most of the compounds used in these studies are used only in basic research and not in clinical studies, which may be a barrier to successful translation into clinical applications
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