Centre of Excellence for Pharmaceutical Sciences, Faculty of Health, North-West University.
Water Research Group, Unit for Environmental Sciences and Management, North-West University, Potchefstroom.
Behav Pharmacol. 2023 Oct 1;34(7):424-436. doi: 10.1097/FBP.0000000000000750. Epub 2023 Aug 24.
Cognitive rigidity (CR) refers to inadequate executive adaptation in the face of changing circumstances. Increased CR is associated with a number of psychiatric disorders, for example, obsessive-compulsive disorder, and improving cognitive functioning by targeting CR in these conditions, may be fruitful. Levetiracetam (LEV), clinically used to treat epilepsy, may have pro-cognitive effects by restoring balance to neuronal signalling. To explore this possibility, we applied apomorphine (APO) exposure in an attempt to induce rigid cue-directed responses following a cue (visual pattern)-reward (social conspecifics) contingency learning phase and to assess the effects of LEV on such behaviours. Briefly, zebrafish were divided into four different 39-day-long exposure groups ( n = 9-10) as follows: control (CTRL), APO (100 µg/L), LEV (750 µg/L) and APO + LEV (100 µg/L + 750 µg/L). The main findings of this experiment were that 1) all four exposure groups performed similarly with respect to reward- and cue-directed learning over the first two study phases, 2) compared to the CTRL group, all drug interventions, but notably the APO + LEV combination, lowered the degree of reward-directed behaviour during a dissociated presentation of the cue and reward, and 3) temporal and spatial factors influenced the manner in which zebrafish responded to the presentation of the reward. Future studies are needed to explore the relevance of these findings for our understanding of the potential cognitive effects of LEV.
认知僵化(CR)是指在面对变化的环境时,执行能力适应不足。越来越多的证据表明,CR 与许多精神疾病有关,例如强迫症,通过针对这些疾病中的 CR 来改善认知功能可能是富有成效的。左乙拉西坦(LEV)临床上用于治疗癫痫,通过恢复神经元信号的平衡可能具有认知促进作用。为了探索这种可能性,我们应用了阿扑吗啡(APO)暴露,试图在线索(视觉模式)-奖励(社会同物种)条件学习阶段之后诱导僵化的线索导向反应,并评估 LEV 对这些行为的影响。简而言之,将斑马鱼分为四个不同的 39 天暴露组(n=9-10),分别为:对照组(CTRL)、APO(100μg/L)、LEV(750μg/L)和 APO+LEV(100μg/L+750μg/L)。这项实验的主要发现是:1)所有四个暴露组在前两个学习阶段的奖励和线索导向学习方面表现相似;2)与对照组相比,所有药物干预,特别是 APO+LEV 联合用药,降低了在分离呈现线索和奖励时奖励导向行为的程度;3)时空因素影响了斑马鱼对奖励呈现的反应方式。需要进一步的研究来探索这些发现对我们理解 LEV 的潜在认知作用的相关性。