Ratano Patrizia, Palmery Maura, Trezza Viviana, Campolongo Patrizia
Department of Physiology and Pharmacology, Sapienza University of RomeRome, Italy.
Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre UniversityRome, Italy.
Front Pharmacol. 2017 Apr 12;8:200. doi: 10.3389/fphar.2017.00200. eCollection 2017.
The effects induced by exogenous manipulation of endocannabinoid neurotransmission on emotion and memory are often contradictory. Among the different factors involved, of particular interest is the binding affinity of endocannabinoids, and their analogs, for other receptor families beyond cannabinoid receptors, such as the peroxisome proliferator-activated receptors (PPARs), and the transient receptor potential cation channel subfamily V member 1 (TRPV1). The aim of this study was to investigate which receptor subtype mediates cannabinoid effects on memory consolidation for emotionally arousing experiences. We tested two cannabinoid compounds with different pharmacological properties in the inhibitory avoidance task, and evaluated whether the observed effects are mediated by cannabinoid, PPARα or TRPV1 receptor activation. We found that the synthetic cannabinoid agonist WIN55,212-2 and the FAAH inhibitor URB597 both enhanced memory consolidation for inhibitory avoidance training. WIN55,212-22 effects on memory consolidation were predominantly mediated by CB1 receptor activation but CB2 receptors were involved as well. The URB597-induced memory enhancement was dependent on the activation not only of CB1 and CB2 receptors but, notwithstanding, PPAR-α and TRPV1 receptors were involved as well. Our findings drive beyond the classical hypothesis centered on the unique role of CB1 receptor activation for cannabinoid effects on memory, and reveal new insights in the neural mechanisms of memory consolidation.
内源性大麻素神经传递的外源性调控对情绪和记忆产生的影响往往相互矛盾。在涉及的不同因素中，特别值得关注的是内源性大麻素及其类似物对除大麻素受体之外的其他受体家族的结合亲和力，如过氧化物酶体增殖物激活受体（PPARs）和瞬时受体电位阳离子通道亚家族V成员1（TRPV1）。本研究的目的是探究哪种受体亚型介导大麻素对情绪唤起体验的记忆巩固作用。我们在抑制性回避任务中测试了两种具有不同药理特性的大麻素化合物，并评估观察到的效应是否由大麻素、PPARα或TRPV1受体激活介导。我们发现，合成大麻素激动剂WIN55,212-2和脂肪酸酰胺水解酶（FAAH）抑制剂URB597均增强了抑制性回避训练的记忆巩固。WIN55,212-2对记忆巩固的作用主要由CB1受体激活介导，但CB2受体也参与其中。URB597诱导的记忆增强不仅依赖于CB1和CB2受体的激活，尽管如此，PPAR-α和TRPV1受体也参与其中。我们的研究结果超越了以CB1受体激活对大麻素记忆效应的独特作用为中心的经典假说，并揭示了记忆巩固神经机制的新见解。
