Department of Physiology and Pharmacology, Sapienza University of Rome, P.le A. Moro 5, Rome, Italy.
Neuropsychopharmacology. 2013 Jun;38(7):1276-86. doi: 10.1038/npp.2013.26. Epub 2013 Jan 22.
Although it is well established that cannabinoid drugs can influence cognitive performance, the findings-describing both enhancing and impairing effects-have been ambiguous. Here, we investigated the effects of posttraining systemic administration of the synthetic cannabinoid agonist WIN55,212-2 (0.1, 0.3, or 1.0 mg/kg) on short- and long-term retention of object recognition memory under two conditions that differed in their training-associated arousal level. In male Sprague-Dawley rats that were not previously habituated to the experimental context, WIN55,212-2 administered immediately after a 3-min training trial, biphasically impaired retention performance at a 1-h interval. In contrast, WIN55,212-2 enhanced 1-h retention of rats that had received extensive prior habituation to the experimental context. Interestingly, immediate posttraining administration of WIN55,212-2 to non-habituated rats, in doses that impaired 1-h retention, enhanced object recognition performance at a 24-h interval. Posttraining WIN55,212-2 administration to habituated rats did not significantly affect 24-h retention. In light of intimate interactions between cannabinoids and the hypothalamic-pituitary-adrenal axis, we further investigated whether cannabinoid administration might differently influence training-induced glucocorticoid activity in rats in these two habituation conditions. WIN55,212-2 administered after object recognition training elevated plasma corticosterone levels in non-habituated rats whereas it decreased corticosterone levels in habituated rats. Most importantly, following pretreatment with the corticosterone-synthesis inhibitor metyrapone, WIN55,212-2 effects on 1- and 24-h retention of non-habituated rats became similar to those seen in the low-aroused habituated animals, indicating that cannabinoid-induced regulation of adrenocortical activity contributes to the environmentally sensitive effects of systemically administered cannabinoids on short- and long-term retention of object recognition memory.
尽管已经证实大麻素药物会影响认知表现，但这些发现——描述了增强和损害的效果——一直存在歧义。在这里，我们研究了在两种不同的训练相关唤醒水平条件下，训练后系统给予合成大麻素激动剂 WIN55,212-2（0.1、0.3 或 1.0mg/kg）对短期和长期物体识别记忆保留的影响。在未适应实验环境的雄性 Sprague-Dawley 大鼠中，WIN55,212-2 在 3 分钟训练试验后立即给药，在 1 小时的间隔内呈双相损害保留表现。相比之下，WIN55,212-2 增强了对实验环境有广泛适应的大鼠 1 小时的保留。有趣的是，立即在非适应大鼠中给予 WIN55,212-2 后，以损害 1 小时保留的剂量给药，增强了 24 小时的物体识别表现。WIN55,212-2 在适应的大鼠中给予训练后，对 24 小时保留没有显著影响。鉴于大麻素和下丘脑-垂体-肾上腺轴之间的密切相互作用，我们进一步研究了大麻素给药是否会以不同的方式影响这两种适应条件下大鼠训练诱导的糖皮质激素活性。WIN55,212-2 在物体识别训练后给药会增加非适应大鼠的血浆皮质酮水平，而降低适应大鼠的皮质酮水平。最重要的是，在用皮质酮合成抑制剂甲吡酮预处理后，WIN55,212-2 对非适应大鼠 1 小时和 24 小时保留的影响变得与低唤醒适应动物相似，表明大麻素诱导的肾上腺皮质活性调节有助于环境敏感效应系统给予大麻素对短期和长期物体识别记忆保留的影响。
