Yim T T, Hong N S, Ejaredar M, McKenna J E, McDonald R J
Canadian Centre for Behavioural Neuroscience, Department of Psychology and Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada T1K 3M4.
Neuroscience. 2008 Feb 19;151(4):929-36. doi: 10.1016/j.neuroscience.2007.08.037. Epub 2007 Dec 4.
Cannabinoids have long been associated with mnemonic deficits. However, existing evidence has generally focused on the effect of cannabinoids when they are delivered prior to task-training, and such findings are confounded by possible drug effects on sensory, motor, and/or motivational systems that support the acquisition and the expression of learning. The present study investigated the effects of the CB1-receptor agonist WIN 55,212-2 (WIN) on memory consolidation in the Morris water maze. In experiment 1, systemic injections of either WIN or DMSO vehicle were given daily following each training day (post-training), and rats were probe-tested 1 week or 4 weeks later. Rats injected with 1 mg/kg and 3 mg/kg of WIN spent significantly less time in the target quadrant compared with controls 4 weeks later, while no difference was observed at 1-week retention. In experiment 2, intrahippocampal injections of WIN were administered to the dorsal hippocampus following each training day and rats were again probe-tested 1 week or 4 weeks later. Rats bilaterally infused with WIN at 2.5 microg and 5 microg (per side) during training spent significantly less time in the target quadrant than vehicle controls on probe trial 4 weeks later, while no difference was seen at 1-week retention. Taken together, our results showed that post-training activation of CB1 receptors in the hippocampus disrupts long-term memory consolidation but has no effect on acquisition and short-term retention. Plausible pharmacological interactions between cannabinoids and other neurotransmitter systems and associated plasticity mechanisms are discussed.
大麻素长期以来一直与记忆缺陷有关。然而，现有证据通常集中在任务训练前给予大麻素的效果上，而这些发现因药物对支持学习获取和表达的感觉、运动和/或动机系统可能产生的影响而受到混淆。本研究调查了CB1受体激动剂WIN 55,212-2（WIN）对莫里斯水迷宫中记忆巩固的影响。在实验1中，在每个训练日之后（训练后）每天进行WIN或二甲基亚砜载体的全身注射，1周或4周后对大鼠进行探测测试。与对照组相比，注射1mg/kg和3mg/kg WIN的大鼠在4周后在目标象限花费的时间明显减少，而在1周的记忆保持期未观察到差异。在实验2中，在每个训练日之后向背侧海马体进行WIN的海马内注射，1周或4周后再次对大鼠进行探测测试。在训练期间双侧注入2.5μg和5μg（每侧）WIN的大鼠在4周后的探测试验中在目标象限花费的时间明显少于载体对照组，而在1周的记忆保持期未观察到差异。综上所述，我们的结果表明，训练后海马体中CB1受体的激活会破坏长期记忆巩固，但对获取和短期记忆保持没有影响。本文还讨论了大麻素与其他神经递质系统之间可能存在的药理学相互作用以及相关的可塑性机制。
