Chen Liangpei, Huang Shihao, Yang Chang, Wu Feilong, Zheng Qiuyao, Yan He, Yan Jie, Luo Yixiao, Galaj Ewa
Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China.
Department of Forensic Science, School of Basic Medical Science, Central South University, Changsha, China.
Front Pharmacol. 2021 May 25;12:686845. doi: 10.3389/fphar.2021.686845. eCollection 2021.
Persistent traces of drug reward memories contribute to intense craving and often trigger relapse. A number of pharmacological interventions on drug-associated memories have shown significant benefits in relapse prevention at a preclinical level but their translational potential is limited due to deleterious side effects. Propranolol, a non-specific β-adrenergic receptors antagonist, is known for its ability to erase maladaptive memories associated with nicotine or cocaine in rodents and humans. However, little is known about its effect on reconsolidation of heroin memory and heroin seeking. In the present study, rats with a history of intravenous heroin self-administration received the propranolol treatment (10 mg/kg; i.p.) at different time windows with or without CS (conditioned stimulus) exposure. Our results showed that propranolol, when administered immediately after CS exposure but not 6 h later, can significantly attenuate cue-induced and drug-primed reinstatement of heroin seeking, suggesting that propranolol has the ability to disrupt heroin memory and reduce relapse. The propranolol treatment without retrieval of drug memory had no effect on subsequent reinstatement of heroin seeking, suggesting that its interfering effects are retrieval-dependent. Importantly, the effects of propranolol were long lasting as rats showed diminished drug seeking even 28 days after the treatment. Altogether, our study suggests that propranolol can interfere with reconsolidation of heroin memory and reduce subsequent drug seeking, making it an attractive therapeutic candidate for the treatment of opioid addiction and relapse prevention.
药物奖赏记忆的持续痕迹会导致强烈的渴望，并常常引发复吸。一些针对与药物相关记忆的药理学干预在临床前水平的复吸预防中显示出显著益处，但由于有害的副作用，它们的转化潜力有限。普萘洛尔是一种非特异性β-肾上腺素能受体拮抗剂，以其能够消除啮齿动物和人类中与尼古丁或可卡因相关的适应不良记忆而闻名。然而，关于其对海洛因记忆巩固和海洛因觅求的影响却知之甚少。在本研究中，有静脉注射海洛因自我给药史的大鼠在不同时间窗口接受普萘洛尔治疗（10毫克/千克；腹腔注射），同时伴有或不伴有条件刺激（CS）暴露。我们的结果表明，普萘洛尔在CS暴露后立即给药而非6小时后给药时，能够显著减弱线索诱导和药物引发的海洛因觅求恢复，这表明普萘洛尔有能力破坏海洛因记忆并减少复吸。未检索药物记忆的普萘洛尔治疗对随后的海洛因觅求恢复没有影响，这表明其干扰作用依赖于记忆检索。重要的是，普萘洛尔的作用是持久的，因为大鼠在治疗后甚至28天仍表现出海洛因觅求减少。总之，我们的研究表明普萘洛尔可以干扰海洛因记忆的巩固并减少随后的药物觅求，使其成为治疗阿片类成瘾和预防复吸的有吸引力的治疗候选药物。
