Adrenal-dependent diurnal modulation of conditioned fear extinction learning.
Adrenal-dependent diurnal modulation of conditioned fear extinction learning.
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DOI：
10.1016/j.bbr.2015.03.006
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发表时间：
2015-06-01
影响因子：
2.7
通讯作者：
Spencer, Robert L.
中科院分区：
文献类型：
--
作者：
Woodruff, Elizabeth R.;Greenwood, Benjamin N.;Chun, Lauren E.;Fardi, Sara;Hinds, Laura R.;Spencer, Robert L.
创伤后应激障碍（PTSD）与改变的条件性恐惧消退表达和受损的昼夜节律功能（包括糖皮质激素分泌失调）相关。我们在成年雄性大鼠中研究了条件性恐惧消退学习、昼夜节律和内源性糖皮质激素（CORT）之间的关系。在大鼠的活跃或非活跃昼夜节律阶段期间施用的3个单独的每日阶段（条件性恐惧获得和2个消退阶段）中训练和测试维持在12小时光：暗周期的大鼠。在最初的实验中，我们发现，在两个昼夜节律阶段的大鼠获得和熄灭的听觉线索条件的恐惧在第一次灭绝会议相似的程度。然而，在Zeitgeber时间-16（ZT 16）（活跃期）训练和测试的大鼠在第二次消退期间与在ZT 4（非活跃期）训练和测试的大鼠相比表现出增强的消退记忆表达。在后续实验中，肾上腺切除（ADX）或假手术大鼠在ZT 4或ZT 16的3个单独的每日阶段中进行类似的训练和测试。ADX对条件性恐惧获得和条件性恐惧记忆没有影响。与所有其他组大鼠相比，在ZT 16训练和测试的假ADX大鼠在两个消退阶段表现出更好的消退学习。这些结果表明，条件性恐惧消退学习是由一天中的时间调制，这种昼夜调制需要肾上腺激素的存在。这些结果支持了CORT依赖的昼夜节律过程在调节条件性恐惧消退学习中的重要作用，这可能被用来优化PTSD的有效治疗。
Post Traumatic Stress Disorder (PTSD) is associated with altered conditioned fear extinction expression and impaired circadian function including dysregulation of glucocorticoid hormone secretion. We examined in adult male rats the relationship between conditioned fear extinction learning, circadian phase, and endogenous glucocorticoids (CORT). Rats maintained on a 12 hr light:dark cycle were trained and tested across 3 separate daily sessions (conditioned fear acquisition and 2 extinction sessions) that were administered during either the rats’ active or inactive circadian phase. In an initial experiment we found that rats at both circadian phases acquired and extinguished auditory cue conditioned fear to a similar degree in the first extinction session. However, rats trained and tested at zeitgeber time-16 (ZT16) (active phase) showed enhanced extinction memory expression during the second extinction session compared to rats trained and tested at ZT4 (inactive phase). In a follow-up experiment, adrenalectomized (ADX) or sham surgery rats were similarly trained and tested across 3 separate daily sessions at either ZT4 or ZT16. ADX had no effect on conditioned fear acquisition or conditioned fear memory. Sham ADX rats trained and tested at ZT16 exhibited better extinction learning across the two extinction sessions compared to all other groups of rats. These results indicate that conditioned fear extinction learning is modulated by time of day, and this diurnal modulation requires the presence of adrenal hormones. These results support an important role of CORT-dependent circadian processes in regulating conditioned fear extinction learning, which may be capitalized upon to optimize effective treatment of PTSD.
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DOI：
10.1523/jneurosci.2173-12.2012
发表时间：
2012-10-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Barrientos RM;Hein AM;Frank MG;Watkins LR;Maier SF
通讯作者：
Maier SF
影响因子：
5.3
作者：
Mizoguchi, K;Ishige, A;Tabira, T
通讯作者：
Tabira, T
影响因子：
4
作者：
Owens, DS;Macdonald, I;Folkard, S
通讯作者：
Folkard, S
影响因子：
2.7
作者：
Perez-Cruz, Claudia;Simon, Maria;Czeh, Boldizsar
通讯作者：
Czeh, Boldizsar
影响因子：
25
作者：
Eckel-Mahan, Kristin L.;Phan, Trongha;Han, Sung;Wang, Hongbing;Chan, Guy C-K;Scheiner, Zachary S.;Storm, Daniel R.
通讯作者：
Storm, Daniel R.