The comorbidities of depression and chronic pain have long been recognized in the clinic, and several preclinical studies have demonstrated depression-like behaviors in animal models of chronic pain. These findings suggest a common neuronal basis for depression and chronic pain. Recently, we reported that the mesolimbic dopaminergic system was tonically suppressed during chronic pain by enhanced inhibitory synaptic inputs to neurons projecting from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area (VTA), suggesting that tonic suppression of the mesolimbic dopaminergic system by this neuroplastic change may be involved in chronic pain-induced depression-like behaviors. In this study, we hypothesized that inhibitory synaptic inputs to VTA-projecting dlBNST neurons are also enhanced in animal models of depression, thereby suppressing the mesolimbic dopaminergic system. To test this hypothesis, we performed whole-cell patch-clamp electrophysiology using brain slices prepared from rats exposed to chronic mild stress (CMS), a widely used animal model of depression. The results showed a significant enhancement in the frequency of spontaneous inhibitory postsynaptic currents in VTA-projecting dlBNST neurons in the CMS group compared with the no stress group. The findings revealed enhanced inhibitory synaptic inputs to VTA-projecting dlBNST neurons in this rat model of depression, suggesting that this neuroplastic change is a neuronal mechanism common to depression and chronic pain that causes dysfunction of the mesolimbic dopaminergic system, thereby inducing depression-like behaviors.

中文翻译：

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在暴露于慢性轻度应激的大鼠中，突触传递到投射到腹侧被盖区的终末纹状体神经元的床核的抑制性突触传递得以增强。

长期以来，抑郁症和慢性疼痛的合并症已在临床上得到认可，一些临床前研究表明，在慢性疼痛的动物模型中，抑郁症的行为类似。这些发现提示抑郁和慢性疼痛的常见神经元基础。最近，我们报道说，在慢性疼痛期间，中音边缘的多巴胺能系统被增强的抑制性突触输入（从纹状体的背外侧床核（dlBNST）投射到腹侧被盖区（VTA）的神经元）在声调上被抑制，这表明对强直中神经边缘的多巴胺能多巴胺能系统的这种改变可能参与了慢性疼痛引起的抑郁样行为。在这个研究中，我们假设在抑郁症动物模型中，向VTA投射dlBNST神经元的抑制性突触输入也得到了增强，从而抑制了中脑边缘的多巴胺能系统。为了验证这一假设，我们使用从暴露于慢性轻度应激（CMS）（一种广泛使用的抑郁动物模型）的大鼠制备的脑片进行了全细胞膜片钳电生理检查。结果表明，与无压力组相比，CMS组中投射VTA的dlBNST神经元中自发抑制突触后电流的频率显着增加。研究结果显示，在这种抑郁症大鼠模型中，VTA投射dlBNST神经元的抑制性突触输入增加，