Delta/mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression: assessment of therapeutic index in male Sprague Dawley rats.
Delta/mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression: assessment of therapeutic index in male Sprague Dawley rats.
复制标题
DOI：
10.1007/s00213-018-4876-x
复制
发表时间：
2018-05
影响因子：
3.4
通讯作者：
Stevenson GW
中科院分区：
文献类型：
--
作者：
Cone K;Lanpher J;Kinens A;Richard P;Couture S;Brackin R;Payne E;Harrington K;Rice KC;Stevenson GW
尽管δ/μ受体相互作用作为行为终点的函数而变化，但是还没有使用疼痛抑制反应测定来评估这些相互作用。这是第一次报告的delta/mu的相互作用，使用的测定疼痛抑郁的行为。一个多周期的FR 10操作时间表中使用的存在下（伤害性）和（率抑制）的乳酸炎性疼痛样操作的情况下。SNC 80和美沙酮分别用作选择性/高效δ和μ激动剂。SNC 80和美沙酮单独使用均产生剂量依赖性的疼痛抑制反应恢复和剂量依赖性的反应率抑制。三个固定比例的混合物，基于在伤害感受试验中药物的相对效力，也产生剂量依赖性的抗伤害感受和镇静。等辐射线分析表明，所有三种混合物产生超加性抗伤害作用和简单的加性镇静作用。治疗指数（TI）作为混合物中SNC 80的量的函数而反向变化，使得较低量的SNC 80产生较高的TI，并且较大量产生较低的TI。与使用标准疼痛诱发测定的文献相比，本文报道的SNC 80和TI之间的有序关系可能是评估疼痛抑制行为的独特功能。
Although delta/mu receptor interactions vary as a function of behavioral endpoint, there have been no assessments of these interactions using assays of pain-depressed responding. This is the first report of delta/mu interactions using an assay of pain depressed behavior. A mult-cycle FR10 operant schedule was utilized in the presence of (nociception) and in the absence of (rate suppression) a lactic acid inflammatory pain-like manipulation. SNC80 and methadone were used as selective/high efficacy delta and mu agonists, respectively. Both SNC80 and methadone alone produced dose-dependent restoration of pain-depressed responding and dose-dependent response rate suppression. Three fixed ratio mixtures, based on the relative potencies of the drugs in the nociception assay, also produced dose-dependent antinociception and sedation. Isobolographic analysis indicated that all three mixtures produced supra-additive antinociceptive effects and simply additive sedation effects. The therapeutic index (TI) inversely varied as a function of amount of SNC80 in the mixture, such that lower amounts of SNC80 produced a higher TI, and larger amounts produced a lower TI. Compared to literature using standard pain-elicited assays, the orderly relationship between SNC80 and TI reported here, may be a unique function of assessing pain-depressed behavior.
登录
查看更多内容
影响因子：
7.4
作者：
Negus SS;Neddenriep B;Altarifi AA;Carroll FI;Leitl MD;Miller LL
通讯作者：
Miller LL
影响因子：
5.7
作者：
Lemberg, Kim;Kontinen, Vesa K.;Kalso, Eija
通讯作者：
Kalso, Eija
影响因子：
3.1
作者：
Erbs E;Faget L;Scherrer G;Matifas A;Filliol D;Vonesch JL;Koch M;Kessler P;Hentsch D;Birling MC;Koutsourakis M;Vasseur L;Veinante P;Kieffer BL;Massotte D
通讯作者：
Massotte D
DOI：
10.1124/jpet.114.219873
发表时间：
2015-02-01
影响因子：
3.5
作者：
Altarifi, Ahmad A.;Rice, Kenner C.;Negus, S. Stevens
通讯作者：
Negus, S. Stevens
影响因子：
8.8
作者：
Martin, TJ;Buechler, NL;Eisenach, JC
通讯作者：
Eisenach, JC