Effects of URB597 as an inhibitor of fatty acid amide hydrolase on WIN55, 212-2-induced learning and memory deficits in rats
Effects of URB597 as an inhibitor of fatty acid amide hydrolase on WIN55, 212-2-induced learning and memory deficits in rats
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DOI：
10.1016/j.pbb.2015.02.007
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发表时间：
2015-04-01
影响因子：
3.6
通讯作者：
Far, Massoud Teimuri
中科院分区：
文献类型：
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作者：
Hasanein, Parisa;Far, Massoud Teimuri
大麻素和内源性大麻素系统与多种生理功能有关，包括认知调节。在这项研究中，我们使用物体识别和被动回避学习 (PAL) 测试评估了脂肪酸酰胺水解酶 (FAAH) 抑制剂 URB597 和 CBI 受体激动剂 WIN55, 212-2 对记忆的影响和相互作用。在获得试验前 30 分钟施用 WIN 55,212-2（1 mg/kg，腹腔注射）诱导学习和记忆障碍。在WIN 55、212-2或URB597前10分钟分别向大鼠注射URB597（0.1、0.3和1mg/kg，Lp.）或SR141716A（1mg/kg，Lp.）。 1JRB597（0.3 和 1 mg/kg）而非 0.1 mg/kg 在物体识别测试中诱导更高的辨别指数（DI），并在 PAL 测试中增强记忆获取。 URB597 的认知增强作用被 CB1 受体拮抗剂 SRI 41716A 阻断，单独使用该剂量对认知没有影响。 WIN55、212-2 在两项测试中均导致认知缺陷。 URB597（0.3 和 1 mg/kg）治疗可以减轻 WIN 55,212-2 对认知和记忆的负面影响。这些结果表明 URB597 具有防止大麻素引起的记忆缺陷的潜力。因此，结合 URB597 的有益作用，本研究表明 URB597 具有识别和习得记忆增强作用。它还可能构成一种治疗大麻素引起的记忆缺陷的新方法，并有助于更好地理解认知背后的大脑机制。 (C) 2015 Elsevier Inc. 保留所有权利。
cannabinoid and endocannabinoid systems have been implicated in several physiological functions including modulation of cognition. In this study we evaluated the effects and interaction between fatty-acid amide hydrolase (FAAH) inhibitor URB597 and CBI receptor agonist WIN55, 212-2 on memory using object recognition and passive avoidance learning (PAL) tests. Learning and memory impairment was induced by WIN 55,212-2 administration (1 mg/kg, i.p.) 30 min before the acquisition trial. URB597 (0.1, 0.3 and 1 mg/kg, Lp.) or SR141716A (1 mg/kg, Lp.) was injected to rats 10 min before WIN 55, 212-2 or URB597 respectively. 1JRB597 (0.3 and 1 mg/kg) but not 0.1 mg/kg induced higher discrimination index (DI) in object recognition test and enhanced memory acquisition in PAL test. The cognitive enhancing effect of URB597 was blocked by a CB1 receptor antagonist, SRI 41716A which at this dose alone had no effect on cognition. WIN55, 212-2 caused cognition deficits in both tests. URB597 (0.3 and 1 mg/kg) treatment could alleviate the negative influence of WIN 55,212-2 on cognition and memory. These results indicate URB597 potential to protect against memory deficits induced by cannabinoid. Therefore, in combination with URB597 beneficial effects, this study suggests that URB597 has recognition and acquisition memory enhancing effects. It may also constitute a novel approach for the treatment of cannabinoid induced memory deficits and lead to a better understanding of the brain mechanisms underlying cognition. (C) 2015 Elsevier Inc. All rights reserved.