Bilateral Inhibition of [gamma]-Aminobutyric Acid Type A Receptor Function within the Basolateral Amygdala Blocked Propofol-induced Amnesia and Activity-regulated Cytoskeletal Protein Expression Inhibition in the Hippocampus.
Ren, Yu Ph.D. *; Zhang, Fu-Jun M.D. +; Xue, Qing-Sheng M.D., Ph.D. ++; Zhao, Xin Ph.D. ++; Yu, Bu-Wei M.D., Ph.D. [S]
基底杏仁核区γ-氨基丁酸A型受体功能的双侧抑制：阻滞丙泊酚引起的遗忘及其引起的活性调节的海马区细胞骨架蛋白的表达抑制。
有研究证明BLA的双侧损坏可阻断丙泊酚引起的IA训练后遗忘。基于这些研究，作者提出假说认为丙泊酚引起的遗忘部分是由于通过活化BLAγ-氨基丁酸A型受体功能而导致的海马区记忆形成破坏。作者以Arc表达变化作为IA记忆形成的指示物。以雄性Sprague-Dawley大鼠为模型，通过实验证明大剂量甲碘荷包牡丹碱不但可以阻断丙泊酚引起的遗忘还可逆转丙泊酚引起的海马区Arc蛋白表达。得出结论，丙泊酚引起的遗忘部分是通过与BLA的网状联系进而调节Arc蛋白表达实现的。

Abstract
Background: It has been reported that bilateral lesions of the basolateral amygdala complex (BLA) blocked propofol-induced amnesia of inhibitory avoidance (IA) training. Based on these results, the authors hypothesized that the amnesia effect of propofol was partly due to its impairment of memory formation in the hippocampus through activating the BLA γ-aminobutyric acid type A receptor function. The authors determined the changes in activity-regulated cytoskeleton-associated protein (Arc) expression to be an indicator of IA memory formation.
Methods: Male Sprague-Dawley rats received bilateral injection of bicuculline methiodide (10, 50, or 100 pmol/0.5 μl) or saline (0.5 μl) into the BLA. Fifteen minutes later, the rats were intraperitoneally injected with either propofol (25 mg/kg) or saline. After 5 min, the one-trial IA training was conducted. Rats intraperitoneally infused with saline served as controls and only received saline injections into the BLA. Twenty-four hours later, the IA retention latency was tested. Separate groups of rats treated the same way were killed either 30 min after IA training for hippocampal Arc mRNA measurement or after 45 min for protein level quantification.
Results: The largest dose of bicuculline methiodide (100 pmol) not only blocked the propofol-induced amnesia but also reversed the inhibition effect of propofol on Arc protein expression in the hippocampus (P < 0.05). However, the mRNA level of Arc showed no significant changes after propofol and bicuculline methiodide administration.
Conclusions: The amnesic effect of propofol seems to involve the modulation of Arc protein expression in the hippocampus, occurring through a network interaction with the BLA.