Dept. of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Physiol Behav. 2012 Mar 20;105(5):1168-74. doi: 10.1016/j.physbeh.2011.12.016. Epub 2011 Dec 28.
Recent research investigating Pavlovian fear conditioning and fear extinction has elucidated the neurocircuitry involved in acquisition and inhibition of fear responses. Modulatory factors that may underlie individual differences in fear acquisition and inhibition, however, are not well understood. Testosterone is known to affect anxiety-like behavior and cognitive processing. In this study, we hypothesized that castration would increase anxiety and reduce memory for contextual fear conditioning in an age-dependent manner. In addition, castration would reduce the rate of extinction to context, as high levels of testosterone correlate with reduced PTSD-like symptoms. We compared behaviors in male mice that were castrated at one of two different time points, either before puberty (at 4 weeks) or after puberty (at 10 weeks) to sham-operated control mice. The behaviors investigated included: anxiety, cued and contextual fear conditioning, and extinction of the fear memory. An interaction of hormone status and age and a significant effect of age were measured in the elevated plus maze, a measure of anxiety. Castration caused a significant reduction of contextual fear memory, but no effect on cued fear memory. There was no significant effect of castration on extinction. Interestingly, a significant effect of age of the mouse at the time of testing was observed on extinction. These results suggest that endogenous androgens during puberty are important for anxiety and fear memory formation. In addition, these results define a late post-adolescent developmental time point for changes in anxiety and fear extinction.
最近的研究调查了巴甫洛夫恐惧条件反射和恐惧消退，阐明了涉及恐惧反应获得和抑制的神经回路。然而，对于导致恐惧获得和抑制个体差异的调节因素，我们还了解甚少。睾酮已知会影响焦虑样行为和认知加工。在这项研究中，我们假设去势会以年龄依赖的方式增加焦虑并减少对情境恐惧条件反射的记忆。此外，去势会降低对情境的消退率，因为高水平的睾酮与 PTSD 样症状的减少有关。我们比较了在两个不同时间点去势的雄性小鼠（分别在青春期前（4 周）或青春期后（10 周））和假手术对照小鼠的行为。研究的行为包括：焦虑、条件性和情境性恐惧条件反射，以及恐惧记忆的消退。在高架十字迷宫中测量了激素状态和年龄的相互作用以及年龄的显著影响，这是焦虑的一种衡量标准。去势导致情境性恐惧记忆显著减少，但对条件性恐惧记忆没有影响。去势对消退没有显著影响。有趣的是，在测试时小鼠的年龄对消退有显著影响。这些结果表明，青春期内的内源性雄激素对焦虑和恐惧记忆的形成很重要。此外，这些结果定义了焦虑和恐惧消退的青春期后晚期发育时间点的变化。
