Effects of the delta-opioid agonist SNC80 on the abuse liability of methadone in rhesus monkeys: a behavioral economic analysis
Effects of the delta-opioid agonist SNC80 on the abuse liability of methadone in rhesus monkeys: a behavioral economic analysis
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DOI：
10.1007/s00213-011-2235-2
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发表时间：
2011-08-01
影响因子：
3.4
通讯作者：
Negus, S. Stevens
中科院分区：
文献类型：
--
作者：
Banks, Matthew L.;Roma, Peter G.;Negus, S. Stevens
原理：阿片受体激动剂可以增强美沙酮和其他阿片受体激动剂的抗伤害感受效果。然而，对于delta受体激动剂可能增强mu受体激动剂滥用相关效应的程度，人们知之甚少。目的采用行为经济学方法，在药物自我给药试验中考察δ受体激动剂SNC80 [(+)-4-[(α R)- α -（(2S,5R)-4-烯丙基-2,5-二甲基-1-哌嗪基）-3-甲氧基苄基]- N，N-二乙基苯酰胺]对美沙酮强化作用的影响。SNC80和可卡因之间的相互作用也进行了比较。方法对4只手术植入留置静脉导管的恒河猴进行两期试验。在一期试验中，在固定比10 （FR 10）强化方案下，测定了美沙酮（0.0032-0.1 mg/kg/注射（inj））和可卡因（0.0032-0.32 mg/kg/注射）单独给药的剂量效应曲线。在第二阶段，在单独使用美沙酮（0.032 mg/kg/inj）、与不同比例的SNC80（0.1:1、0.3:1和0.9:1 SNC80/美沙酮）或单独使用可卡因（0.032 mg/kg/inj）和与不同比例的SNC80（0.33:1、1:1和3:1 SNC80/可卡因）时，FR值每3天增加一次（FR 1-FR 1800）。推导了药物摄入与FR价格之间的需求曲线，并给出了强化措施。结果美沙酮和可卡因均有强化作用。SNC80没有改变美沙酮或可卡因的强化措施。结论SNC80在先前的研究中可增强美沙酮诱导的抗痛觉作用，但并未增强美沙酮的滥用相关效应。这些结果支持了delta受体激动剂可以选择性地增强受体激动剂的镇痛作用，而不会增加受体激动剂滥用的可能性。
Rationale Delta-opioid agonists enhance the antinociceptive efficacy of methadone and other mu-opioid agonists. However, relatively little is known about the degree to which delta agonists might enhance the abuse-related effects of mu agonists.Objective This study used a behavioral economic approach to examine effects of the delta agonist SNC80 [(+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N,N-diethylbenzamide] on the reinforcing effects of methadone in a drug self-administration assay. Interactions between SNC80 and cocaine were also examined for comparison.Methods Rhesus monkeys (n=4), surgically implanted with indwelling intravenous catheters, were tested in two phases. In phase 1, drug self-administration dose-effect curves for methadone (0.0032-0.1 mg/kg/injection (inj)) and cocaine (0.0032-0.32 mg/kg/inj) alone were determined under a fixed-ratio 10 (FR 10) schedule of reinforcement. In phase 2, FR values were increased every 3 days (FR 1-FR 1800) during availability of methadone alone (0.032 mg/kg/inj) and in combination with varying proportions of SNC80 (0.1:1, 0.3:1, and 0.9:1 SNC80/methadone) or of cocaine alone (0.032 mg/kg/inj) and in combination with varying proportions of SNC80 (0.33:1, 1: 1, and 3: 1 SNC80/cocaine). Demand curves related drug intake to FR price, and measures of reinforcement were derived.Results Methadone and cocaine alone each functioned as a reinforcer. SNC80 did not alter measures of reinforcement for either methadone or cocaine.Conclusions SNC80 at proportions previously shown to enhance methadone-induced antinociception did not enhance the abuse-related effects of methadone. These results support the proposition that delta agonists may selectively enhance mu agonist analgesic effects without enhancing mu agonist abuse liability.