Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Brain Res. 2011 May 4;1388:69-76. doi: 10.1016/j.brainres.2011.02.086. Epub 2011 Mar 5.
Exposure of newborn rats to antiepileptics such as barbiturates has long-lasting detrimental effects on the hippocampus and hippocampus-dependent behavior. However, the long-term consequences of neonatal administration with barbiturates on the hippocampal synaptic plasticity remain unresolved. In this study, we investigated the long-lasting effects of a neonatal administration of pentobarbital on spatial memory, paired-pulse plasticity in the population spikes, and long-term potentiation (LTP) in the hippocampal CA1 region of rats in vivo. Eight weeks after administration of pentobarbital (10 or 20mg/kg) on the seventh postnatal day (P7), rats showed impaired induction in LTP. During paired-pulse stimulation, pentobarbital-treated rats exhibited a greater facilitation of the test pulse population spike, suggesting a disruption in the inhibitory GABAergic synaptic transmission. Spatial learning in hidden platform task of the Morris water maze was impaired in pentobarbital-treated rats. Our present findings indicate that neonatal treatment with pentobarbital causes alterations in function of the hippocampal inhibitory synaptic transmission that persist into adulthood, likely contributing to the long-lasting abnormalities in the hippocampal LTP as well as learning ability. We also demonstrated significant respiratory disturbances, i.e., severe hypoxia, hypercapnia, and extracellular acidosis, in rats treated with pentobarbital on P7. Given that extracellular acidosis can also modulate synaptic transmission in the developing hippocampus, this finding led us to speculate regarding the influence of respiratory disturbances in pentobarbital-induced long-lasting hippocampal dysfunctions.
新生大鼠暴露于苯巴比妥等抗癫痫药物中会对海马体及其依赖海马体的行为产生持久的不利影响。然而，新生期给予苯巴比妥对海马突触可塑性的长期后果仍未得到解决。在这项研究中，我们研究了新生期给予戊巴比妥对大鼠体内空间记忆、群体峰电流的成对脉冲可塑性和海马 CA1 区长时程增强（LTP）的长期影响。在第 7 天（P7）给予戊巴比妥（10 或 20mg/kg）后 8 周，大鼠的 LTP 诱导能力受损。在成对脉冲刺激期间，戊巴比妥处理的大鼠表现出测试脉冲群体峰电流的更大易化，提示抑制性 GABA 能突触传递中断。在隐蔽平台任务的 Morris 水迷宫中的空间学习能力在戊巴比妥处理的大鼠中受损。我们目前的发现表明，新生期给予戊巴比妥会导致海马体抑制性突触传递功能发生改变，这种改变持续到成年期，可能导致海马体 LTP 以及学习能力的持久异常。我们还在 P7 时给予戊巴比妥的大鼠中观察到明显的呼吸紊乱，即严重缺氧、高碳酸血症和细胞外酸中毒。鉴于细胞外酸中毒也可以调节发育中的海马体中的突触传递，这一发现促使我们推测呼吸紊乱对戊巴比妥诱导的长期海马功能障碍的影响。
