Conrad Cheryl D, MacMillan Donald D, Tsekhanov Sergey, Wright Ryan L, Baran Sarah E, Fuchs Rita A
Department of Psychology, Arizona State University, Box 1104, Tempe, AZ 85287-1104, USA.
Neurobiol Learn Mem. 2004 May;81(3):185-99. doi: 10.1016/j.nlm.2004.01.002.
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 microg/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 (20s) and footshock (500 ms, 0.25 mA) pairings. In Experiment 1, muscimol (4.4 nmol/0.5 microl/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 microl/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.
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皮质酮的大鼠的增强反应。雄性Sprague-Dawley大鼠在饮用水中摄入皮质酮（400微克/毫升）（第1 - 21天），先前的一项操作表明这种处理会导致海马CA3树突回缩。随后，大鼠适应恐惧条件反射箱（第22天），然后进行训练（第23天），并测试对环境和音调的条件性恐惧（第25天）。训练包括两次音调（20秒）和足部电击（500毫秒，0.25毫安）配对。在实验1中，在训练期间微量注射GABA能激动剂蝇蕈醇（4.4纳摩尔/0.5微升/侧）以暂时使BLA失活。与补充赋形剂的大鼠相比，给予慢性皮质酮的大鼠对环境的僵住反应增强，但对音调的僵住反应未增强。此外，无论皮质酮处理如何，BLA失活都会损害环境和音调条件反射。在实验2中，在训练当天注入RU486（0、0.3和3.0纳克/0.2微升/侧）以拮抗BLA中的糖皮质激素受体。综合分析时，皮质酮处理增强了对环境和音调的恐惧条件反射，但分别分析时则不然。此外，RU486（3.0纳克/侧）仅选择性地加剧了慢性暴露于皮质酮的大鼠对环境的僵住反应，但未改变音调条件反射。血清皮质酮水平与环境条件反射呈负相关，与音调条件反射无关。总之，这些结果表明，慢性皮质酮对恐惧条件反射的影响与先前所示的慢性应激不同。此外，长期暴露于皮质类固醇会以非线性方式改变BLA的功能，并且慢性皮质酮和BLA糖皮质激素受体刺激对环境条件反射的影响比对音调条件反射的影响更大。
