PDF(Pubmed)
Abstract：
Effective treatments for major depressive disorder (MDD) have long been needed. One hypothesis for the mechanism of depression involves a decrease in neuroactive steroids such as allopregnanolone, an endogenous positive allosteric modulator of the γ-aminobutyric acid-gated chloride channel (GABAA) receptor. In our previous study, we discovered that allopregnanolone, not diazepam, exhibited antidepressant-like effects in the social interaction test (SIT) of social defeat stress (SDS) model mice. However, the dynamics of neuronal activity underlying the antidepressant-like effect remain unknown. In the current study, we conducted local field potentials (LFPs) recordings from the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) during the SIT to elucidate the relationship between the antidepressant-like effect and neuronal oscillation. We discovered that allopregnanolone has antidepressant-like effects in the SIT of SDS model mice by decreasing intervals of repetitive social interaction (inter-event intervals), resulting in increase of total social interaction time. We also found that theta and beta oscillation increased in BLA at the onset of social interaction following administration of allopregnanolone, which differed from the effects of diazepam. Theta and beta power in BLA within the social interaction zone exhibited a positive correlation with interaction time. This increase of theta and beta power was negatively correlated with inter-event intervals. Regarding theta-band coordinated activity between the BLA and mPFC, theta power correlation decreased at the onset of social interaction with the administration of allopregnanolone. These findings suggest that theta activity in BLA following social interaction and the reduced theta-band coordinated activity between the BLA and mPFC are implicated in social interaction, which is one of the antidepressant behaviors. These differences in neural activity could elucidate the distinctive mechanism underlying antidepressant-like effects of neuroactive steroids, as opposed to benzodiazepines.
摘要：
长期以来，人们一直需要对重度抑郁症（MDD）进行有效的治疗。抑郁症机制的一个假设涉及神经活性类固醇如别孕烷醇酮的减少，γ-氨基丁酸门控氯通道（GABAA）受体的内源性正变构调节剂。在我们之前的研究中,我们发现了别孕烷醇酮,不是地西泮,在社交失败应激（SDS）模型小鼠的社交互动测试（SIT）中表现出抗抑郁样作用。然而,抗抑郁药样效应背后的神经元活动的动力学仍然未知.在目前的研究中,我们在SIT期间从基底外侧杏仁核(BLA)和内侧前额叶皮质(mPFC)进行了局部场电位(LFP)记录,以阐明抗抑郁样效应与神经元振荡之间的关系.我们发现，在SDS模型小鼠的SIT中，通过减少重复社会互动的间隔（事件间间隔），导致社会互动总时间增加。我们还发现，在服用别孕烷醇酮后，在社会互动开始时，BLA中的θ和β振荡增加，这与地西泮的效果不同。社交互动区域内BLA的θ和β功率与互动时间呈正相关。θ和β功率的增加与事件间间隔呈负相关。关于BLA和mPFC之间的θ带协调活性，在使用别孕烯醇酮进行社交互动时，θ功率相关性降低。这些发现表明，社会互动后BLA中的theta活动以及BLA和mPFC之间减少的theta带协调活动与社会互动有关。这是抗抑郁行为之一。神经活性的这些差异可以阐明神经活性类固醇抗抑郁样作用的独特机制，而不是苯二氮卓类药物。
