Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, T2N 4N1, Canada.
Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada.
Behav Brain Res. 2020 Sep 1;393:112747. doi: 10.1016/j.bbr.2020.112747. Epub 2020 Jun 3.
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.
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，并被研究用于抗癫痫。由于 Z944 会影响失神性癫痫模型啮齿动物的恐惧学习和记忆，因此确定 Z944 在非疾病近交系啮齿动物中的学习和记忆中的作用非常重要。本研究检查了急性全身性给予 Z944 的剂量依赖性作用（5 mg/kg、10 mg/kg，ip）对雄性 Wistar 大鼠恐惧条件反射和消退的学习和记忆的影响。在恐惧条件反射获得之前给予 Z944 处理显著增加了获得前、获得期间和获得后 24 小时恐惧记忆回忆时的冻结行为。这些发现表明，T 型钙通道活性可能在完整的长期记忆的联想学习过程中是必需的。在获得前和获得期间以及获得期间观察到的增强的恐惧行为可能反映了焦虑的增加，但是，需要进一步的测试来确定 Z944 在恐惧条件反射和消退期间对焦虑的影响。出于治疗目的使用 Z944 时，应考虑 Z944 对临床人群学习和记忆的潜在影响。
