Department of Physiology, Nanjing Medical University, Hanzhong Road 140, Jiangsu, PR China.
Neuroscience. 2010 Oct 27;170(3):749-57. doi: 10.1016/j.neuroscience.2010.07.055. Epub 2010 Aug 3.
Prenatal exposure to a relatively high-dose ethanol (EtOH) caused anxiety-like behavior of adult male rat offspring. Previous studies have demonstrated that GABA system in the basolateral amygdala complex (BLA) is involved in the pathogensis of anxiety-related disorders. The role of GABAergic system in the BLA was investigated in anxiety-like behavior evoked by prenatal EtOH exposure. The infusion of midazolam (MDZ), a positive modulator of GABA(A) receptor, into the BLA prevented anxiety-like behavior in EtOH-offspring without affecting the corresponding behavior of control offspring. The data suggest that anxiety-like behavior could be causally related to increased neuronal excitability attributable to depressed GABAergic inhibition in the BLA. To test this hypothesis, evoked potential was studied using brain slices from EtOH-offspring. Potential evoked in the BLA by single stimuli applied to external capsule showed multispike responses, indicative of GABAergic disinhibition. These multiple responses were no longer evident after the perfusion with MDZ. In the slices from EtOH-offspring, paired-pulse inhibition (GABA(A)-dependent) was suppressed. Also, in EtOH-offspring, long-term potentiation (LTP) was induced by a single train of high frequency stimulation, which did not induce LTP in control rats. Moreover, MDZ pretreatment prevented the facilitating effect of EtOH on LTP induction. The data provide the functional evidence that prenatal EtOH exposure attenuates GABAergic inhibition in the BLA resulting in neuronal hyperexcitability and anxiety-like behavior of adult rat offspring.
产前暴露于相对高剂量的乙醇（EtOH）可导致成年雄性大鼠后代出现类似焦虑的行为。先前的研究表明，外侧杏仁核复合体（BLA）中的 GABA 系统参与了焦虑相关障碍的发病机制。本研究旨在探讨 BLA 中的 GABA 能系统在产前 EtOH 暴露引起的类似焦虑行为中的作用。将咪达唑仑（MDZ）——一种 GABA（A）受体的正变构调节剂——输注到 BLA 中可预防 EtOH 后代的类似焦虑行为，而不影响对照后代的相应行为。数据表明，类似焦虑的行为可能与 BLA 中 GABA 能抑制作用降低导致的神经元兴奋性增加有关。为了验证这一假设，本研究使用来自 EtOH 后代的脑片研究了诱发电位。用单刺激施加于外囊时，BLA 中诱发的电位显示出多峰反应，表明 GABA 能去抑制。这些多峰反应在 MDZ 灌注后不再明显。在 EtOH 后代的脑片中，成对脉冲抑制（GABA（A）依赖性）受到抑制。此外，在 EtOH 后代中，单个高频刺激串可诱导长时程增强（LTP），而在对照大鼠中则不能诱导 LTP。此外，MDZ 预处理可预防 EtOH 对 LTP 诱导的促进作用。这些数据提供了功能证据，表明产前 EtOH 暴露可减弱 BLA 中的 GABA 能抑制作用，导致神经元过度兴奋和成年大鼠后代出现类似焦虑的行为。
