Melo António, Leite-Almeida Hugo, Ferreira Clara, Sousa Nuno, Pêgo José M
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of MinhoBraga, Portugal; ICVS/3B's - PT Government Associate LaboratoryBraga/Guimarães, Portugal.
Front Behav Neurosci. 2016 Nov 24;10:226. doi: 10.3389/fnbeh.2016.00226. eCollection 2016.
: Ketamine is a general anesthetic (GA) that activates several neurotransmitter pathways in various part of the brain. The acute effects as GA are the most well-known and sought-after: to induce loss of responsiveness and to produce immobility during invasive procedures. However, there is a concern that repeated exposure might induce behavioral changes that could outlast their acute effect. Most research in this field describes how GA affects cognition and memory. Our work is to access if general anesthesia with ketamine can disrupt the motivational behavior trait, more specifically measuring impulsive behavior. : Aiming to evaluate the effects of exposure to repeat anesthetic procedures with ketamine in motivational behavior, we tested animals in a paradigm of impulsive behavior, the variable delay-to-signal (VDS). In addition, accumbal and striatal medium spiny neurons morphology was assessed. : Our results demonstrated that previous exposure to ketamine deep-anesthesia affects inhibitory control (impulsive behavior). Specifically, ketamine exposed animals maintain a subnormal impulsive rate in the initial periods of the delays. However, in longer delays while control animals progressively refrain their premature unrewarded actions, ketamine-exposed animals show a different profile of response with higher premature unrewarded actions in the last seconds. Animals exposed to multiple ketamine anesthesia also failed to show an increase in premature unrewarded actions between the initial and final periods of 3 s delays. These behavioral alterations are paralleled by an increase in dendritic length of medium spiny neurons of the nucleus accumbens (NAc). : This demonstrates that ketamine anesthesia acutely affects impulsive behavior. Interestingly, it also opens up the prospect of using ketamine as an agent with the ability to modulate impulsivity trait.
氯胺酮是一种全身麻醉剂,可激活大脑不同部位的多种神经递质通路。作为全身麻醉剂,其急性作用最为人所知且备受关注:在侵入性手术过程中诱导反应丧失和产生不动状态。然而,人们担心反复接触可能会导致行为改变,且这种改变可能会持续超过其急性作用的时间。该领域的大多数研究描述了全身麻醉如何影响认知和记忆。我们的工作是研究氯胺酮全身麻醉是否会扰乱动机行为特征,更具体地说是测量冲动行为。
为了评估反复使用氯胺酮进行麻醉程序对动机行为的影响,我们在一种冲动行为范式——可变信号延迟(VDS)中对动物进行了测试。此外,还评估了伏隔核和纹状体中等棘状神经元的形态。
我们的结果表明,先前接受氯胺酮深度麻醉会影响抑制控制(冲动行为)。具体而言,接受氯胺酮处理的动物在延迟的初始阶段保持低于正常的冲动率。然而,在较长延迟期间,当对照动物逐渐抑制其过早的无奖励行为时,接受氯胺酮处理的动物表现出不同的反应模式,在最后几秒有更高的过早无奖励行为。接受多次氯胺酮麻醉的动物在3秒延迟的初始和最终阶段之间也未能表现出过早无奖励行为的增加。这些行为改变与伏隔核(NAc)中等棘状神经元树突长度的增加平行。
这表明氯胺酮麻醉会急性影响冲动行为。有趣的是,这也开启了将氯胺酮用作一种能够调节冲动特质的药物的前景。