Lorcaserin Suppresses Oxycodone Self-Administration and Relapse Vulnerability in Rats.
Lorcaserin Suppresses Oxycodone Self-Administration and Relapse Vulnerability in Rats.
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DOI：
10.1021/acschemneuro.6b00413
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发表时间：
2017-05-17
影响因子：
5
通讯作者：
Cunningham KA
中科院分区：
文献类型：
--
作者：
Neelakantan H;Holliday ED;Fox RG;Stutz SJ;Comer SD;Haney M;Anastasio NC;Moeller FG;Cunningham KA
阿片使用障碍(OUD)是一个主要的公共卫生问题。较高的复发率和较差的治疗保留率继续构成OUD治疗的主要挑战。在被滥用的阿片类药物中，羟考酮被很好地描述为维持自我管理并唤起持久的条件性反应(“线索反应”)，这是由于与阿片类药物相关的刺激(例如，用具)与反复滥用配对而产生的。5-羟色胺(5-HT)神经传递，特别是通过5-HT2C受体(5-HT2CR)，调节精神刺激奖赏和线索反应性，在目前的实验中，我们调查了FDA批准用于治疗肥胖的选择性5-HT2CR激动剂氯酪蛋白将抑制大鼠羟考酮自身给药和羟考酮相关线索反应性的假说。我们发现氯卡瑟林抑制羟考酮的摄取，这种作用被选择性的5-HT2CR拮抗剂SB242084阻断。在戒断和消退-恢复模型中，氯酪蛋白也降低了对先前与羟考酮(即刺激灯、输液泵声音)传递相关的离散线索复合体(“线索反应性”)的反应。在本研究中，氯酪蛋白的选定剂量范围(0.25-1 mg/kg)不会明显改变自发行为，也不会改变对非活动杠杆的可操作性反应。综上所述，氯酪蛋白能够减少羟考酮的自我给药和降低与复发相关的线索反应性，这突显了氯酪蛋白在治疗OUD方面的治疗潜力。
Opioid use disorder (OUD) is a major public health problem. High relapse rates and poor treatment retention continue to pose major challenges in OUD treatment. Of the abused opioids, oxycodone is well described to maintain self-administration and evoke the durable conditioned responses (“cue reactivity”) that result from pairing of opioid-related stimuli (e.g., paraphernalia) with repeated abuse. Serotonin (5-HT) neurotransmission, particularly through the 5-HT2C receptor (5-HT2CR), regulates psychostimulant reward and cue reactivity, and in the present experiments, we investigated the hypothesis that the selective 5-HT2CR agonist lorcaserin, which is FDA-approved for the treatment of obesity, will suppress oxycodone self-administration and oxycodone-associated cue reactivity in rats. We found that lorcaserin inhibited oxycodone intake, an effect blocked by the selective 5-HT2CR antagonist SB242084. Lorcaserin also decreased responding for the discrete cue complex (“cue reactivity”) previously associated with delivery of oxycodone (i.e., stimulus lights, infusion pump sounds) in both abstinence and extinction-reinstatement models. The selected dose range of lorcaserin (0.25–1 mg/kg) does not overtly alter spontaneous behaviors nor operant responding on inactive levers in the present study. Taken together, the ability of lorcaserin to reduce the oxycodone self-administration and decrease cue reactivity associated with relapse highlights the therapeutic potential for lorcaserin in the treatment of OUD.