BACKGROUND Growing evidence suggests that mechanical stimulation modulates substrates in the supraspinal central nervous system (CNS) outside the canonical somatosensory circuits. OBJECTIVE/METHODS We evaluate mechanical stimulation applied to the cervical spine at the C7-T1 level (termed "MStim") on neurons and neurotransmitter release in the mesolimbic dopamine (DA) system, an area implicated in reward and motivation, utilizing electrophysiological, pharmacological, neurochemical and immunohistochemical techniques in Wistar rats. RESULTS Low frequency (45-80 Hz), but not higher frequency (115 Hz), MStim inhibited the firing rate of ventral tegmental area (VTA) GABA neurons (52.8% baseline; 450 s) while increasing the firing rate of VTA DA neurons (248% baseline; 500 s). Inactivation of the nucleus accumbens (NAc), or systemic or in situ antagonism of delta opioid receptors (DORs), blocked MStim inhibition of VTA GABA neuron firing rate. MStim enhanced both basal (178.4% peak increase at 60 min) and evoked DA release in NAc (135.0% peak increase at 40 min), which was blocked by antagonism of DORs or acetylcholine release in the NAc. MStim enhanced c-FOS expression in the NAc, but inhibited total expression in the VTA, and induced translocation of DORs to neuronal membranes in the NAc. CONCLUSION These findings demonstrate that MStim modulates neuron firing and DA release in the mesolimbic DA system through endogenous opioids and acetylcholine in the NAc. These findings demonstrate the need to explore more broadly the extra-somatosensory effects of peripheral mechanoreceptor activation and the specific role for mechanoreceptor-based therapies in the treatment of substance abuse.

中文翻译：

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颈椎的机械刺激调节腹侧被盖区神经元的放电活动和伏核中的多巴胺释放

背景越来越多的证据表明，机械刺激在规范的躯体感觉回路之外调节脊髓上中枢神经系统（CNS）中的底物。目的/方法我们评估了在 C7-T1 水平（称为“MStim”）对颈椎施加的机械刺激对神经元和中脑边缘多巴胺 (DA) 系统中的神经递质释放的影响，中脑边缘多巴胺 (DA) 系统是一个与奖励和动机有关的区域，利用电生理学、药理学, Wistar 大鼠的神经化学和免疫组织化学技术。结果 低频 (45-80 Hz)，但不是更高频率 (115 Hz)，MStim 抑制腹侧被盖区 (VTA) GABA 神经元的放电率（52.8% 基线；450 秒），同时增加 VTA DA 神经元的放电率（248% 基线；500 秒）。伏隔核（NAc）失活，或全身或原位拮抗 delta 阿片受体 (DOR)，阻断 MStim 对 VTA GABA 神经元放电率的抑制。MStim 增强了 NAc 中的基础（60 分钟峰值增加 178.4%）和诱发 DA 释放（40 分钟峰值增加 135.0%），这被 NAc 中 DOR 或乙酰胆碱释放的拮抗作用阻断。MStim 增强了 NAc 中 c-FOS 的表达，但抑制了 VTA 中的总表达，并诱导了 DOR 易位到 NAc 中的神经元膜。结论这些发现表明，MStim 通过内源性阿片类物质和 NAc 中的乙酰胆碱调节中脑边缘 DA 系统中的神经元放电和 DA 释放。