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T-type calcium channels regulate the acquisition and recall of conditioned fear in male, Wistar rats.
Behavioural Brain Research ( IF 2.7 ) Pub Date : 2020-06-03 , DOI: 10.1016/j.bbr.2020.112747
Wendie N Marks 1 , Nadine K Zabder 2 , Terrance P Snutch 3 , John G Howland 2
Affiliation  

The T-type calcium channel blocker, Z944, has been used as a pharmacological tool to assess T-type calcium channel function and examined for use as an anti-epileptic. As Z944 affects fear learning and memory in a rodent model of absence epilepsy, it is important to determine the effect of Z944 on learning and memory in a non-disease outbred rodent strain. This study examined the dose-dependent effects (5 mg/kg, 10 mg/kg, i.p.) of acute systemic treatment with Z944 on the learning and memory of fear conditioning and extinction in male Wistar rats. Z944 administered prior to the acquisition of fear conditioning significantly increased freezing prior to acquisition and extinction, during acquisition, and impaired recall of fear memory 24 h later. These findings suggest that T-type calcium channel activity may be required during associative learning for intact long-term memory. Enhanced fear behaviour observed prior to acquisition and extinction, and during acquisition could reflect an increase in anxiety, however, further testing is needed to determine the effect of Z944 on anxiety during fear conditioning and extinction. The use of Z944 for therapeutic purposes should consider the potential effects of Z944 on learning and memory in clinical populations.



中文翻译:

T 型钙通道调节雄性 Wistar 大鼠条件恐惧的获得和回忆。

T 型钙通道阻滞剂 Z944 已被用作评估 T 型钙通道功能的药理学工具,并已被用作抗癫痫药。由于 Z944 影响失神癫痫啮齿动物模型中的恐惧学习和记忆,因此确定 Z944 对非疾病远交啮齿动物品系学习和记忆的影响很重要。本研究检查了 Z944 急性全身治疗对雄性 Wistar 大鼠恐惧条件反射和灭绝的学习和记忆的剂量依赖性影响(5 mg/kg、10 mg/kg、ip)。在获得恐惧条件反射之前施用 Z944 显着增加了获得和消退之前、获得过程中的冻结,并在 24 小时后对恐惧记忆的回忆受损。这些发现表明,在联想学习过程中可能需要 T 型钙通道活动才能获得完整的长期记忆。在获得和灭绝之前以及获得期间观察到的增强的恐惧行为可能反映焦虑的增加,但是,需要进一步测试以确定 Z944 对恐惧条件反射和灭绝期间焦虑的影响。将 Z944 用于治疗目的应考虑 Z944 对临床人群学习和记忆的潜在影响。

更新日期:2020-06-03
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