Khanegheini A, Nasehi M, Zarrindast M-R
Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
Institute for Cognitive Science Studies (ICSS), Tehran, Iran; Cognitive and Neuroscience Research Center (CNRC), Medical Genomics Research Center and School of Advanced Sciences in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.
Neuroscience. 2015 Oct 1;305:157-68. doi: 10.1016/j.neuroscience.2015.07.083. Epub 2015 Aug 5.
Glutamate and γ-aminobutyric acid (GABA) are among the most abundant neurotransmitters in the central nervous system. Ketamine and other noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists are known to induce deficits in learning and the performance of cognitive tasks. The present study was designed to assess the effects of dorsal hippocampal (CA1) GABAb receptors on ketamine-induced spatial and non-spatial memory deficits with regard to the role of Ca(2+) as a defining factor. Spatial and non-spatial novelty detection of male NMRI mice were investigated in a circular open-field apparatus. According to our results, the intraperitoneal injection of ketamine at its higher dose (0.1 mg/kg) impaired both spatial and non-spatial novelty detection. Moreover, the intra-CA1 injection of baclofen (a GABAb receptor agonist) at higher doses (0.02 and 0.2 μg/mouse) impaired the spatial but not non-spatial novelty detection. In addition, phaclofen (a GABAb receptor antagonist at 0.2 μg/mouse) impaired both spatial and non-spatial novelty detection. Baclofen restored and induced a modulatory effect on ketamine-induced responses in the spatial and non-spatial novelty detection task, respectively. On the contrary, phaclofen restored and induced a modulatory effect on ketamine-induced responses in the non-spatial and spatial novelty detection task, respectively. Finally, the subthreshold dose of SKF96365 (a Ca(2+) channel blocker) impaired only the spatial but not non-spatial restoration effects of baclofen or phaclofen following a higher dose of ketamine. Such findings suggest that the ketamine-induced impairment of memory consolidation may occur through GABAb receptors of the CA1 neurons. Moreover, baclofen and phaclofen were shown to possibly exert their effects on the ketamine-induced spatial novelty detection deficits through Ca(2+) channels.
谷氨酸和γ-氨基丁酸（GABA）是中枢神经系统中含量最为丰富的神经递质。已知氯胺酮和其他非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂会导致学习和认知任务表现方面的缺陷。本研究旨在评估背侧海马体（CA1）GABAb受体对氯胺酮诱导的空间和非空间记忆缺陷的影响，并将Ca(2+)作为一个决定性因素进行考量。在圆形旷场装置中对雄性NMRI小鼠的空间和非空间新奇性检测进行了研究。根据我们的结果，腹腔注射高剂量（0.1mg/kg）的氯胺酮会损害空间和非空间新奇性检测。此外，在CA1内注射高剂量（0.02和0.2μg/小鼠）的巴氯芬（一种GABAb受体激动剂）会损害空间新奇性检测，但不会损害非空间新奇性检测。另外，注射0.2μg/小鼠的法氯芬（一种GABAb受体拮抗剂）会损害空间和非空间新奇性检测。巴氯芬分别对氯胺酮诱导的空间和非空间新奇性检测任务中的反应具有恢复和调节作用。相反，法氯芬分别对氯胺酮诱导的非空间和空间新奇性检测任务中的反应具有恢复和调节作用。最后，亚阈值剂量的SKF96365（一种Ca(2+)通道阻滞剂）仅损害了高剂量氯胺酮后巴氯芬或法氯芬对空间的恢复作用，而未损害对非空间的恢复作用。这些发现表明，氯胺酮诱导的记忆巩固损害可能通过CA1神经元的GABAb受体发生。此外，巴氯芬和法氯芬可能通过Ca(2+)通道对氯胺酮诱导的空间新奇性检测缺陷发挥作用。
