Acca Gillian M, Mathew Abel S, Jin Jingji, Maren Stephen, Nagaya Naomi
Institute for Neuroscience, Texas A&M University, College Station, TX, USA.
Department of Psychology, Texas A&M University, College Station, TX, USA.
Horm Behav. 2017 Mar;89:137-144. doi: 10.1016/j.yhbeh.2017.01.002. Epub 2017 Jan 16.
Gonadal steroids and their metabolites have been shown to be important modulators of emotional behavior. Allopregnanolone (ALLO), for example, is a metabolite of progesterone that has been linked to anxiety-related disorders such as posttraumatic stress disorder. In rodents, it has been shown to reduce anxiety in a number of behavioral paradigms including Pavlovian fear conditioning. We have recently found that expression of conditioned contextual (but not auditory) freezing in rats can be suppressed by infusion of ALLO into the bed nucleus of the stria terminalis (BNST). To further explore the nature of this effect, we infused ALLO into the BNST of male rats prior to both conditioning and testing. We found that suppression of contextual fear occurred when the hormone was present during either conditioning or testing but not during both procedures, suggesting that ALLO acts in a state-dependent manner within the BNST. A shift in interoceptive context during testing for animals conditioned under ALLO provided further support for this mechanism of hormonal action on contextual fear. Interestingly, infusions of ALLO into the basolateral amygdala produced a state-independent suppression of both conditioned contextual and auditory freezing. Altogether, these results suggest that ALLO can influence the acquisition and expression of fear memories by both state-dependent and state-independent mechanisms.
性腺类固醇及其代谢产物已被证明是情绪行为的重要调节因子。例如，别孕烯醇酮（ALLO）是孕酮的一种代谢产物，它与创伤后应激障碍等焦虑相关疾病有关。在啮齿动物中，已表明它在包括巴甫洛夫恐惧条件反射在内的多种行为范式中可减轻焦虑。我们最近发现，通过将ALLO注入终纹床核（BNST）可抑制大鼠条件性情境性（而非听觉性）僵住反应。为进一步探究这种效应的本质，我们在条件反射和测试之前均将ALLO注入雄性大鼠的BNST。我们发现，当激素在条件反射或测试期间存在但并非在两个过程中都存在时，情境性恐惧会受到抑制，这表明ALLO在BNST内以状态依赖方式起作用。在对在ALLO作用下进行条件反射训练的动物进行测试期间，内感受性情境的转变为激素对情境性恐惧作用的这种机制提供了进一步支持。有趣的是，将ALLO注入基底外侧杏仁核会对条件性情境性和听觉性僵住反应产生与状态无关的抑制作用。总之，这些结果表明ALLO可通过状态依赖和状态无关机制影响恐惧记忆的获取和表达。
