Melamed Jonathan L, de Jesus Fernando M, Maior Rafael S, Barros Marilia
Department of Pharmaceutical Sciences, School of Health Sciences, University of BrasiliaBrasilia, Brazil.
Primate Center and Department of Physiological Sciences, Institute of Biology, University of BrasiliaBrasilia, Brazil.
Front Pharmacol. 2017 Jun 21;8:395. doi: 10.3389/fphar.2017.00395. eCollection 2017.
The non-selective muscarinic receptor antagonist scopolamine (SCP) induces memory deficits in both animals and humans. However, few studies have assessed the effects of amnesic agents on memory functions of marmosets - a small-bodied neotropical primate that is becoming increasingly used as a translational model for several neuropathologies. Here we assessed the effects of an acute SCP administration (0.03 mg/kg, sc) on the behavior of adult marmoset monkeys in two tasks. In the spontaneous object-location (SOL) recognition task, two identical neutral stimuli were explored on the sample trial, after which preferential exploration of the displaced versus the stationary object was analyzed on the test trial. In the fear-motivated behavior (FMB) procedure, the same subjects were submitted to an initial baseline trial, followed by an exposure period to a snake model and lastly a post-exposure trial. All trials and inter-trial intervals lasted 10 min for both tests. Results showed that on the SOL test trial, the saline group explored the displaced object significantly longer than its identical stationary counterpart, whereas SCP-treated marmosets explored both objects equivalently. In the FMB test, the saline group - but not the SCP-treated animals - spent significantly less time where the stimulus had been specifically encountered and more time being vigilant of their surroundings, compared to pre-exposure levels. Drug-related effects on general activity, overall exploration (SOL task) and behavioral response to the aversive stimulus (FMB task) were not observed. SCP thus impaired the marmosets' short-term ability to detect changes associated with the spatial location of ethologically irrelevant (SOL task) and relevant stimuli (FMB task). Similar results have been reported in other animal species. Marmosets may thus help reduce the translational gap between pre-clinical studies and memory-associated human pathologies.
非选择性毒蕈碱受体拮抗剂东莨菪碱(SCP)在动物和人类中均会诱发记忆缺陷。然而,很少有研究评估失忆剂对狨猴记忆功能的影响,狨猴是一种体型较小的新热带灵长类动物,越来越多地被用作多种神经病理学的转化模型。在此,我们评估了急性给予SCP(0.03mg/kg,皮下注射)对成年狨猴在两项任务中行为的影响。在自发物体定位(SOL)识别任务中,在样本试验中探索两个相同的中性刺激,之后在测试试验中分析对移位物体与静止物体的优先探索情况。在恐惧动机行为(FMB)程序中,相同的受试者先进行初始基线试验,接着是接触蛇模型的暴露期,最后是暴露后试验。两项测试的所有试验及试验间隔均持续10分钟。结果显示,在SOL测试试验中,生理盐水组对移位物体的探索时间明显长于其相同的静止对应物,而接受SCP治疗的狨猴对两个物体的探索时间相当。在FMB测试中,与暴露前水平相比,生理盐水组(而非接受SCP治疗的动物)在特定遇到刺激的地方花费的时间显著减少,而对周围环境保持警惕的时间更多。未观察到药物对一般活动、总体探索(SOL任务)和对厌恶刺激的行为反应(FMB任务)的相关影响。因此,SCP损害了狨猴检测与行为学上无关(SOL任务)和相关刺激(FMB任务)的空间位置变化的短期能力。其他动物物种也报告了类似结果。因此,狨猴可能有助于缩小临床前研究与记忆相关人类病理学之间的转化差距。