MedicalResearch.com Interview with:
Lin Lu, M.D. Ph.D.
Director/Professor, Institute of Mental Health and Peking University Sixth Hospital
Director/Professor, National Institute on Drug Dependence, Peking University
MedicalResearch.com: What is the background for this study?
Response: Nicotine addiction is the leading preventable cause of mortality, and causes over 6 million deaths each year. One fundamental mechanism that maintain smoking relapse in smokers is the persistence of memories of both nicotine reward and nicotine-associated conditioned stimulus (CS, e.g. ashtray,cigarette lighters, etc.).Preclinical studies suggest that the drug reward memories can be reactivated by nicotine-associated CS undergo an unstable stage, named memory reconsolidation, and that pharmacological or behavioral manipulations that interfere with reconsolidation inhibit subsequent drug relapse.
However, most of the translational studies targeting reconsolidation stages of the drug reward memory have not been successful.One important reason is that when participants were exposed to nicotine-associated CS to induce memory reconsolidation, the pharmacological or behavioral manipulations only interfere with the reconsolidation of memories selectively associated with the reactivated CS, without affecting other CSs.
However, in real life, smoking is associated with multiple CSs that vary across individuals. Thus, a key question is how to interfere with reconsolidation of multiple nicotine-associated memories . In the present study, we introduce a novel memory reconsolidation interference procedure in which we reactivated multiple nicotine reward memories in rats and human smokers by acute exposure to nicotine (the UCS) and then interfered with memory reconsolidation using the noradrenergic blocker propranolol, an FDA-approved drug.
MedicalResearch.com:What are the main findings?
Response: The findings of this research are that:
(1) In rat models of nicotine addiction, propranolol combination with UCS-triggered but not CS-triggered memory reactivation inhibits subsequent nicotine Pavlovian and instrumental memories, without influencing the acquired memories for a non-drug food reward.
(2) In human smokers, propranolol administration in combination with brief smoking-triggered reactivation of smoking-related memories decreases smokers’ liking for multiple nicotine associated CSs, and reduced their urges to smoke, which was triggered by various smoking-related cues.
(3) In both rats and humans, the pharmacological manipulations have no effect on the different behavioral measures when administered 6-9 h after UCS retrieval (outside the putative ‘reconsolidation’ window), supporting the notion that our manipulations weaken the nicotine maladaptive memories through interfering with memory reconsolidation.
MedicalResearch.com: What should readers take away from your report?
Response: The present rat-to-human translational study demonstrates the efficacy of a combination of UCS memory retrieval and propranolol for inhibiting nicotine craving induced by exposure to diverse nicotine-associated CSs and nicotine itself.The findings across species suggest that the UCS-induced memory retrieval-reconsolidation interference procedures are more promising for prevention of relapse to drug use than the CS-induced procedures.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Our results from rat study and the human smokers study suggest that a UCS-based memory retrieval-reconsolidation interference procedure may be a simple and promising method for preventing nicotine craving and potentially relapse to nicotine addiction. However, the response to nicotine-associated CS is often context-specific. Thus, future studies are needed to test whether the UCS-induced memory retrieval-reconsolidation interference procedure will decrease craving and relapse in the smokers’ home environments.
Additionally, the generalizability of our results is limited because we used only male subjects.Thus, it is needed to test whether the UCS-induced memory retrieval-reconsolidation interference procedure will decrease craving and relapse in the female smokers.
MedicalResearch.com: Is there anything else you would like to add?
Response: The findings from ours (Xue et al., Science, 2012; Xue et al., JAMA Psychiatry, 2017) and other researchers (Germeroth et al., JAMA Psychiatry, 2017) provide evidence that it is feasible to modify maladaptive drug memories during reconsolidation stage, and targeting reconsolidation of drug memories is a promising therapy for substance use disorders.
Any disclosures? No disclosures
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Xue Y, Deng J, Chen Y, Zhang L, Wu P, Huang G, Luo Y, Bao Y, Wang Y, Shaham Y, Shi J, Lu L. Effect of Selective Inhibition of Reactivated Nicotine-Associated Memories With Propranolol on Nicotine Craving. JAMA Psychiatry. Published online February 01, 2017. doi:10.1001/jamapsychiatry.2016.3907
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