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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Conversion of the modulatory actions of dopamine on spinal reflexes from depression to facilitation in D3 receptor knock-out mice.
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Conversion of the modulatory actions of dopamine on spinal reflexes from depression to facilitation in D3 receptor knock-out mice.

机译：在D3受体基因敲除小鼠中，多巴胺对脊髓反射的调节作用从抑郁转变为促进。

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摘要

Descending monoaminergic systems modulate spinal cord function, yet spinal dopaminergic actions are poorly understood. Using the in vitro lumbar cord, we studied the effects of dopamine and D2-like receptor ligands on spinal reflexes in wild-type (WT) and D3-receptor knock-out mice (D3KO). Low dopamine levels (1 microM) decreased the monosynaptic "stretch" reflex (MSR) amplitude in WT animals and increased it in D3KO animals. Higher dopamine concentrations (10-100 microM) decreased MSR amplitudes in both groups, but always more strongly in WT. Like low dopamine, the D3 receptor agonists pergolide and PD 128907 reduced MSR amplitude in WT but not D3KO mice. Conversely, D3 receptor antagonists (GR 103691 and nafadotride) increased the MSR in WT but not in D3KO mice. In comparison, D2-preferring agonists bromocriptine and quinpirole depressed the MSR in both groups. Low dopamine (1-5 microM) also depressed longer-latency (presumably polysynaptic) reflexes in WT but facilitated responses in D3KO mice. Additionally, in some experiments (e.g., during 10 microM dopamine or pergolide in WT), polysynaptic reflexes were facilitated in parallel to MSR depression, demonstrating differential modulatory control of these reflex circuits. Thus, low dopamine activates D3 receptors to limit reflex excitability. Moreover, in D3 ligand-insensitive mice, excitatory actions are unmasked, functionally converting the modulatory action of dopamine from depression to facilitation. Restless legs syndrome (RLS) is a CNS disorder involving abnormal limb sensations. Because RLS symptoms peak at night when dopamine levels are lowest, are relieved by D3 agonists, and likely involve increased reflex excitability, the D3KO mouse putatively explains how impaired D3 activity could contribute to this sleep disorder.
机译：下降的单胺能系统调节脊髓功能，但对脊髓多巴胺能的作用知之甚少。使用体外腰带，我们研究了多巴胺和D2样受体配体对野生型（WT）和D3受体敲除小鼠（D3KO）脊髓反射的影响。低多巴胺水平（1 microM）降低了野生动物的单突触“拉伸”反射（MSR）幅度，并增加了D3KO动物的单突触“拉伸”反射（MSR）幅度。两组中较高的多巴胺浓度（10-100 microM）均降低了MSR幅度，但在WT中始终更为强烈。像低多巴胺一样，D3受体激动剂培高利特和PD 128907降低了WT小鼠的MSR幅度，但不降低D3KO小鼠。相反，D3受体拮抗剂（GR 103691和那法多利）可增加WT小鼠的MSR，但不会增加D3KO小鼠的MSR。相比之下，两组中首选D2激动剂溴隐亭和喹吡罗抑制了MSR。低的多巴胺（1-5 microM）还可降低WT中较长的潜伏期（可能是多突触）反射，但可促进D3KO小鼠的反应。另外，在一些实验中（例如，在WT中的10μM多巴胺或培高利特期间），与MSR抑制平行地促进了多突触反射，表明了这些反射电路的差分调制控制。因此，低多巴胺会激活D3受体，从而限制反射兴奋性。此外，在对D3配体不敏感的小鼠中，兴奋作用未被掩盖，将多巴胺的调节作用从抑郁状态转变为促进状态。不安腿综合征（RLS）是一种CNS疾病，涉及异常的肢体感觉。由于RLS症状在多巴胺水平最低时在夜间达到高峰，并被D3激动剂缓解，并且可能涉及反射兴奋性增强，因此D3KO小鼠推测性地解释了D3活性受损如何导致这种睡眠障碍。

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