Influence of chronic corticosterone and glucocorticoid receptor antagonism in the amygdala on fear conditioning
Influence of chronic corticosterone and glucocorticoid receptor antagonism in the amygdala on fear conditioning
复制标题
DOI：
10.1016/j.nlm.2004.01.002
复制
发表时间：
2004-05-01
影响因子：
2.7
通讯作者：
Fuchs, RA
中科院分区：
文献类型：
--
作者：
Conrad, CD;MacMillan, DD;Fuchs, RA
在恐惧条件反射过程中，基底外侧杏仁核（BLA）内的糖皮质激素受体激活可能介导长期暴露于应激水平的皮质酮的大鼠的增强。雄性Sprague-Dawley大鼠在其饮用水中接受皮质酮（400 μ g/ml）（第1-21天），这是一种先前显示可引起海马CA 3树突回缩的操作。后来。使大鼠适应恐惧条件室（第22天），然后训练（第23天），并测试对环境和音调的条件恐惧（第25天）。训练包括双音调（20 s）和足电击（500 ms，0.25 mA）配对。在实验1中，蝇蕈醇（4.4 nmol/0.5穆尔/侧），一种GABA能激动剂，在训练过程中被微输注以暂时抑制BLA。与补充溶剂的大鼠相比，给予慢性皮质酮的大鼠表现出对上下文的冻结增强，但不是语气。此外，BLA失活损害上下文和语气条件反射。无论皮质酮治疗。在实验2中，RU 486（0，0.3.和3.0 ng/0.2穆尔/侧）以拮抗BLA中的糖皮质激素受体。皮质酮治疗增强恐惧条件反射的背景和语气一起分析时，但不是单独的。此外，RU 486（3.0纳克/侧）选择性加剧冻结的背景下，慢性皮质酮暴露的大鼠，但未能改变音调条件。血清皮质酮水平呈负相关的上下文，而不是语气，条件反射。总之，这些表明，慢性皮质酮影响恐惧条件反射不同于慢性压力，如前所述。此外，慢性暴露于皮质类固醇改变BLA功能的非线性方式和上下文条件的影响比慢性皮质酮和BLA糖皮质激素受体刺激的音调条件。(C)2004爱思唯尔公司All rights reserved.
Glucocorticoid receptor activation within the basolateral amygdala (BLA) during fear conditioning may mediate enhancement in rats chronically exposed to stress levels of corticosterone. Male Sprague-Dawley rats received corticosterone (400 mug/ml) in their drinking water (days 1-21), a manipulation that was previously shown to cause hippocampal CA3 dendritic retraction. Subsequently. rats were adapted to the fear conditioning chamber (day 22), then trained (day 23), and tested for conditioned fear to context and tone (day 25). Training consisted of two tone (20 s) and footshock (500 ms, 0.25 mA) pairings. In Experiment 1, muscimol (4.4 nmol/0.5 mul/side), a GABAergic agonist, was microinfused to temporarily inactivate the BLA during training. Rats given chronic corticosterone showed enhanced freezing to context, but not tone, compared to vehicle-supplemented rats. Moreover, BLA inactivation impaired contextual and tone conditioning.. regardless of corticosterone treatment. In Experiment 2, RU486 (0, 0.3. and 3.0 ng/0.2 mul/side) was infused on training day to antagonize glucocorticoid receptors in the BLA. Corticosterone treatment enhanced fear conditioning to context and tone when analyzed together, but not separately. Moreover, RU486 (3.0 ng/side) selectively exacerbated freezing to context in chronic corticosterone-exposed rats only, but failed to alter tone conditioning. Serum corticosterone levels were negatively correlated with contextual, not tone, conditioning. Altogether, these suggest that chronic corticosterone influences fear conditioning differently than chronic stress as shown previously. Moreover, chronic exposure to corticosteroids alters BLA functioning in a non-linear fashion and that contextual conditioning is influenced more than tone conditioning by chronic corticosterone and BLA glucocorticoid receptor stimulation. (C) 2004 Elsevier Inc. All rights reserved.