PRENATAL ETHANOL EXPOSURE ATTENUATES GABAergic INHIBITION IN BASOLATERAL AMYGDALA LEADING TO NEURONAL HYPEREXCITABILITY AND ANXIETY-LIKE BEHAVIOR OF ADULT RAT OFFSPRING
PRENATAL ETHANOL EXPOSURE ATTENUATES GABAergic INHIBITION IN BASOLATERAL AMYGDALA LEADING TO NEURONAL HYPEREXCITABILITY AND ANXIETY-LIKE BEHAVIOR OF ADULT RAT OFFSPRING
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DOI：
10.1016/j.neuroscience.2010.07.055
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发表时间：
2010-10-27
期刊：
影响因子：
3.3
通讯作者：
Zhu, X.
中科院分区：
文献类型：
--
作者：
Zhou, R.;Wang, S.;Zhu, X.
产前暴露于相对高剂量乙醇（EtOH）可引起成年雄性大鼠后代的焦虑样行为。以往的研究表明，基底外侧杏仁核复合体（BLA）中的GABA系统参与了焦虑相关障碍的发病机制。研究了gaba能系统在产前EtOH暴露诱发的焦虑样行为中的作用。将GABA(a)受体的正调剂咪达唑仑（MDZ）注入BLA后，可阻止etoh子代的焦虑样行为，而不影响对照组子代的相应行为。这些数据表明，类焦虑行为可能与BLA中gaba能抑制抑制导致的神经元兴奋性增加有因果关系。为了验证这一假设，我们使用etoh后代的大脑切片研究了诱发电位。外包膜单次刺激诱发BLA电位出现多峰反应，提示gaba能去抑制。这些多重反应在MDZ灌注后不再明显。在etoh后代的切片中，对脉冲抑制（GABA(A)依赖）被抑制。在etoh -后代中，单次高频刺激可诱导长期增强（LTP），而对照组大鼠未诱导LIP。此外，MDZ预处理阻止了EtOH对LTP诱导的促进作用。这些数据提供了功能证据，表明产前暴露于EtOH可减弱BLA中gaba能抑制，从而导致成年大鼠后代神经元亢进和焦虑样行为。(c) 2010 ibro。Elsevier Ltd.出版。版权所有。
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 LIP 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. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.