Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat
Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat
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DOI：
10.1007/s00213-006-0589-7
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发表时间：
2007-02-01
影响因子：
3.4
通讯作者：
Parker, Linda A.
中科院分区：
文献类型：
--
作者：
Cross-Mellor, Shelley K.;Ossenkopp, Klaus-Peter;Parker, Linda A.
基本原理内源性大麻素系统在控制恶心和呕吐方面发挥着至关重要的作用。由于内源性大麻素（例如 anandamide）的快速分解和水解，可以通过延长其作用持续时间来增强治疗效果。 目的 本实验评估了不同剂量的脂肪酸酰胺水解酶（FAAH）抑制剂 URB597 单独使用以及与全身给予 anandamide 组合来调节大鼠锂诱导的条件性味觉反应性反应建立的潜力。 材料和方法 在实验 1 中，在调理日，大鼠首先接受注射 0.3 mg/kg URB597、0.15 mg/kg URB597 或媒介物，然后接受第二次注射 anandamide (5 mg/kg) 或媒介物，然后通过口内输注暴露 0.1% 糖精 3 分钟。暴露于糖精后，立即给大鼠注射氯化锂。在三个测试日的每一天，大鼠接受 3 分钟的糖精溶液口腔内输注，并对味觉反应反应进行录像和监测。在实验2中，评估了CB1拮抗剂AM-251预处理对URB597和anandamide诱导的厌恶厌恶的影响。结果单独施用URB597以及与anandamide组合使用可减少由LiCl配对糖精溶液引起的主动排斥反应； AM-251 预处理可逆转这两种效应，表明它们是 CB1 受体介导的。 结论 结果表明，通过 FAAH 抑制剂 URB597 预处理延长 anandamide 的作用，可抑制锂引起的大鼠恶心。
Rationale The endogenous cannabinoid system plays a vital role in the control of nausea and emesis. Because of the rapid breakdown and hydrolysis of endocannabinoids, such as anandamide, the therapeutic effects may be enhanced by prolonging their duration of action.Objective The present experiment evaluated the potential of various doses of URB597, a fatty acid amide hydrolase (FAAH) inhibitor, alone and in combination with systemic administration of anandamide to modulate the establishment of lithium-induced conditioned taste reactivity responses in rats.Materials and methods In experiment 1, on the conditioning day, rats first received an injection of 0.3 mg/kg URB597, 0.15 mg/kg URB597, or vehicle and then received a second injection of anandamide (5 mg/kg) or vehicle, before a 3-min exposure of 0.1% saccharin by intraoral infusion. Immediately after the saccharin exposure, the rats were injected with lithium chloride. On each of three test days, rats received a 3-min intraoral infusion of saccharin solution, and the taste reactivity responses were videotaped and monitored. In experiment 2, the effects of pretreatment with the CB1 antagonist, AM-251, on URB597 and anandamide-induced suppressed aversion was evaluated.Results Administration of URB597 alone and in combination with anandamide reduced active rejection reactions elicited by a LiCl-paired saccharin solution; both effects were reversed by pretreatment with AM-251, suggesting that they were CB1 receptor mediated.Conclusions The results suggest that prolonging the action of anandamide by pretreatment with the FAAH inhibitor, URB597, suppresses lithium-induced nausea in the rat.