Improvement of memory in rodents by the selective CB1 cannabinoid receptor antagonist, SR 141716
Improvement of memory in rodents by the selective CB1 cannabinoid receptor antagonist, SR 141716
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DOI：
10.1007/bf02246352
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发表时间：
1996-07-01
影响因子：
3.4
通讯作者：
Soubrie, P
中科院分区：
文献类型：
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作者：
Terranova, JP;Storme, JJ;Soubrie, P
啮齿类动物的社会短期记忆是基于一个成年同种动物在两个连续的场合下对一个幼年动物的识别。据称，大麻模拟物会引起人类和动物的记忆缺陷。在大脑中，它们主要与CB 1受体结合，大麻素是其内源性配体。SR 141716是CB 1受体的特异性拮抗剂，可剂量依赖性逆转大麻拟似物的生化和药理学作用。更具体地，它拮抗由WIN 55，212 -2和花生四烯酸酰胺诱导的海马长时程增强的抑制，并且当单独给予时，它增加唤醒。本实验研究了SR 141716（0.03 - 3 mg/kg SC）在啮齿动物社会识别试验中促进短期嗅觉记忆的能力。SR 141716在0.1 mg/kg SC的阈值剂量下，在长试验间范式中改善了社会识别。在1 mg/kg剂量下，它拮抗了由追溯抑制引起的记忆障碍。东莨菪碱（0.06 mg/kg IP）可部分逆转其记忆增强作用。此外，SR 141716可降低老年大鼠（0.03-0.1 mg/kg）和小鼠（0.3-1 mg/kg）的记忆缺陷。由于已知SR 141716未表现出任何非CB 1受体介导的药理学活性，因此结果强烈支持CB 1受体阻断在巩固啮齿动物短期记忆中发挥重要作用的概念，并表明内源性大麻素激动剂张力（anandaminergic）可能在遗忘中发挥作用。
Social short-term memory in rodents is based on the recognition of a juvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory deficits in both humans and animals. In the brain, they mainly bind to CB1 receptors for which anandamide is a purported endogenous ligand. SR 141716, a specific antagonist of CB1 receptors, dose-dependently reverses biochemical and pharmacological effects of cannabimimetics. More particularly, it antagonizes the inhibition of hippocampal long-term potentiation induced by WIN 55,212-2 and anandamide, and it increases arousal when given alone. The present experiments study the ability of SR 141716 (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social recognition test in rodents. SR 141716 improved social recognition in a long intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it antagonized the memory disturbance elicited by retroactive inhibition. Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect. Moreover, SR 141716 reduced memory deficit in aged rats (0.03-0.1 mg/kg) and mice (0.3-1 mg/kg). As SR 141716 is not known to exhibit any pharmacological activity which is not mediated by CB1 receptors, the results strongly support the concept that blockade of CB1 receptors plays an important role in consolidation of short-term memory in rodents and suggest there may be a role for an endogenous cannabinoid agonist tone (anandaminergic) in forgetting.