Effects of general anesthetics on the neural activity of the immature nervous system.

我们打算验证咪达唑仑可能对新生大鼠发育中的海马发挥兴奋作用并可能减少镇静作用的假设。我们发现咪达唑仑增加了新生大鼠海马CA3区的细胞内Ca浓度和p CREB表达，但在幼鼠中没有。咪达唑仑的这些兴奋作用被一种NKCC1抑制剂布美他尼所抑制。咪达唑仑对新生大鼠的镇静作用小于对幼鼠的镇静作用。布美他尼增强咪达唑仑对新生大鼠的镇静作用，但对幼鼠没有作用。这些结果表明，GABAA受体介导的兴奋依赖于NKCC1，可能是咪达唑仑对新生大鼠镇静作用减弱的基础。

We intended to test the hypothesis that midazolam may exert excitatory actions on the developing hippocampus and may reduce sedative effects in neonatal rats. We found that midazolam increased intracellular Ca concentration and p CREB expression in the hippocampal CA3 area from neonatal rats but not from young rats. These excitatory effects of midazolam were inhibited by bumetanide, an inhibitor for NKCC1. Midazolam exhibited less sedative actions in neonatal rats compared with in young rats. Bumetanide enhanced sedative effects of midazolam in neonatal but not young rats. These results indicate that GABAA receptor-mediated excitation is dependent on NKCC1 and may underlie the attenuated sedative effects of midazolam in neonatal rats.