Brain and skin blood flow: new animal model for understanding psychiatric disorders and evaluating psychotropic agents

大脑和皮肤血流：了解精神疾病和评估精神药物的新动物模型

• 批准号: nhmrc : 187616
• 负责人: E/Pr William Blessing
• 金额: $ 58.33万
• 依托单位: Flinders University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/brain-skin-blood-psychotropic-agents/96183
• 关键词: Brain; skin; blood; flow; new

We suddenly become pale when we get a fright; cutaneous blood vessels are linked to psychological function. The skin vessel constriction response occurs because special neurochemical pathways in the brain send messages to the spinal cord, and from there messages traverse peripheral sympathetic nerves to constrict the blood vessels in the skin. By measuring skin blood flow in the rabbit ear and the rat tail we have been able to discover the major brain pathway by which the constrict-the-skin-blood-vessels message reaches the spinal cord. The pathway involves the amygdala, a forebrain region important in emotional expression and the raphe nuclei in the medulla oblongata. Drugs which affect psychological function also effect skin blood flow. Ecstasy, the street drug used to induce euphoria also constricts the skin vessels, and, sadly, the body temperature may increase so much that death ensues. Ecstasy vigorously constricts the skin blood vessels in rabbits, and temperature increases. Ecstasy is thought to act on serotonin-containing nerve cells in the brain, releasing serotonin (5-HT) onto special 5-HT2A receptors. Activation of these receptors affects both psychological function and skin blood flow. Modern drugs used to treat schizophrenia, so called atypical antipsychotics like clozapine and olanzapine, are thought to act as antagonists at 5-HT2A receptors in the brain. We were thus very excited when we discovered in our rabbit model that clozapine reverses the skin vasoconstriction induced by ecstasy. This means that we have specific hypotheses concerning the actual brain pathways and neurotransmitters whereby ecstasy and clozapine exert their effects on skin blood flow. Elucidating these pathways in rabbits and rats will provide solid knowledge concerning the mechanism of action of the atypical antipsychotics, and it may well prove possible to use our animal model to predict whether proposed new antipsychotic agents will be therapeutically effective.

当我们受到惊吓时，我们会突然变得苍白;皮肤血管与心理功能有关。皮肤血管收缩反应的发生是因为大脑中的特殊神经化学通路将信息发送到脊髓，并从那里通过外周交感神经收缩皮肤中的血管。通过测量兔子耳朵和老鼠尾巴的皮肤血流量，我们已经能够发现收缩皮肤血管的信息到达脊髓的主要大脑通路。这条通路涉及杏仁核（一个在情绪表达中起重要作用的前脑区域）和延髓的中缝核。影响心理功能的药物也会影响皮肤血液流动。用于引起欣快的街头毒品兴奋也会收缩皮肤血管，可悲的是，体温可能会升高到死亡的程度。兴奋使兔子的皮肤血管剧烈收缩，体温升高。兴奋被认为作用于大脑中含有羟色胺的神经细胞，将5-羟色胺（5-HT）释放到特殊的5-HT 2A受体上。这些受体的激活会影响心理功能和皮肤血流。用于治疗精神分裂症的现代药物，所谓的非典型抗精神病药，如氯氮平和奥氮平，被认为是大脑中5-HT 2A受体的拮抗剂。因此，当我们在兔子模型中发现氯氮平可以逆转摇头丸引起的皮肤血管收缩时，我们非常兴奋。这意味着我们对摇头丸和氯氮平对皮肤血流产生影响的实际大脑通路和神经递质有特定的假设。在兔子和大鼠中阐明这些途径将提供关于非典型抗精神病药物作用机制的坚实知识，并且很可能证明可以使用我们的动物模型来预测拟议的新抗精神病药物是否具有治疗效果。