Rostral and Caudal Ventral Tegmental Area GABAergic Inputs to Different Dorsal Raphe Neurons Participate in Opioid Dependence
Rostral and Caudal Ventral Tegmental Area GABAergic Inputs to Different Dorsal Raphe Neurons Participate in Opioid Dependence
复制标题
头侧和尾侧腹侧被盖区不同中缝背神经元的 GABA 能输入参与阿片类药物依赖性
DOI：
10.1016/j.neuron.2018.12.012
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发表时间：
2019-02-20
期刊：
影响因子：
16.2
通讯作者：
Li, Xiao-Ming
中科院分区：
文献类型：
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作者：
Li, Yue;Li, Chun-Yue;Li, Xiao-Ming
腹侧被盖区（VTA）和中缝背核（DRN）都参与情感控制和奖励相关行为。此外，VTA 和 DRN 的神经元活动受到阿片类药物的调节。然而，从 VTA 到 DRN 的精确回路以及阿片类药物如何调节这些回路仍然未知。在这里，我们发现从 VTA 投射到 DRN 的神经元主要是 GABA 能的。喙侧 VTA (rVTA) GABA 能神经元优先支配 DRN GABA 能神经元，从而抑制 DRN 血清素能神经元。该电路的光遗传学激活会引起厌恶。相比之下，尾侧 VTA (cVTA) GABA 能神经元主要针对 DRN 血清素能神经元，该回路的激活可促进奖励。重要的是，m-阿片受体 (MOP) 在 rVTA -> DRN GABA 能突触处选择性表达，吗啡会抑制突触传递。长期提高 rVTA -> DRN 通路的活性会特异性地中断吗啡诱导的条件性位置偏好。这种阿片类药物调节的抑制回路可能有助于了解吗啡奖赏和依赖性发病机制。
Both the ventral tegmental area (VTA) and dorsal raphe nucleus (DRN) are involved in affective control and reward-related behaviors. Moreover, the neuronal activities of the VTA and DRN are modulated by opioids. However, the precise circuits from the VTA to DRN and how opioids modulate these circuits remain unknown. Here, we found that neurons projecting from the VTA to DRN are primarily GABAergic. Rostral VTA (rVTA) GABAergic neurons preferentially innervate DRN GABAergic neurons, thus disinhibiting DRN serotonergic neurons. Optogenetic activation of this circuit induces aversion. In contrast, caudal VTA (cVTA) GABAergic neurons mainly target DRN serotonergic neurons, and activation of this circuit promotes reward. Importantly, m-opioid receptors (MOPs) are selectively expressed at rVTA -> DRN GABAergic synapses, and morphine depresses the synaptic transmission. Chronically elevating the activity of the rVTA -> DRN pathway specifically interrupts morphine-induced conditioned place preference. This opioid-modulated inhibitory circuit may yield insights into morphine reward and dependence pathogenesis.