Department of Psychology, University of Alberta, P-217 Biological, Sciences Building, Edmonton, Alberta, Canada T6G 2E9.
Hippocampus. 2013 Apr;23(4):278-86. doi: 10.1002/hipo.22086. Epub 2012 Dec 28.
Hippocampal theta rhythm has been associated with a number of behavioral processes, including learning and memory, spatial behavior, sensorimotor integration and affective responses. Suppression of hippocampal theta frequency has been shown to be a reliable neurophysiological signature of anxiolytic drug action in tests using known anxiolytic drugs (i.e., correlational evidence), but only one study to date (Yeung et al. (2012) Neuropharmacology 62:155-160) has shown that a drug with no known effect on either hippocampal theta or anxiety can in fact separately suppress hippocampal theta and anxiety in behavioral tests (i.e., prima facie evidence). Here, we attempt a further critical test of the hippocampal theta model by performing intrahippocampal administrations of the Ih blocker ZD7288, which is known to disrupt theta frequency subthreshold oscillations and resonance at the membrane level but is not known to have anxiolytic action. Intrahippocampal microinfusions of ZD7288 at high (15 µg), but not low (1 µg) doses slowed brainstem-evoked hippocampal theta responses in the urethane anesthetized rat, and more importantly, promoted anxiolytic action in freely behaving rats in the elevated plus maze. Taken together with our previous demonstration, these data provide converging, prima facie evidence of the validity of the theta suppression model.
海马体θ节律与许多行为过程有关，包括学习和记忆、空间行为、感觉运动整合和情感反应。在使用已知的抗焦虑药物进行的测试中，抑制海马体θ频率已被证明是抗焦虑药物作用的可靠神经生理特征（即相关证据），但迄今为止只有一项研究（Yeung 等人，2012 年，神经药理学 62:155-160）表明，一种既没有已知的海马体θ作用也没有已知的焦虑作用的药物实际上可以在行为测试中分别抑制海马体θ和焦虑（即初步证据）。在这里，我们通过进行海马体腔内给予 Ih 阻断剂 ZD7288 的进一步关键测试来尝试对海马体θ模型进行进一步测试，已知 ZD7288 会破坏膜水平上的θ频率亚阈值振荡和共振，但没有抗焦虑作用。在乌拉坦麻醉大鼠中，高剂量（15μg）而非低剂量（1μg）的海马体腔内微注射 ZD7288 会减缓脑干诱发的海马体θ反应，更重要的是，在自由行为的大鼠中，在高架十字迷宫中促进了抗焦虑作用。这些数据与我们之前的研究结果一起，提供了θ抑制模型有效性的一致的、初步的证据。
