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

当我们受到惊吓时，我们的脸色会突然变得苍白；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特殊的神经化学路径将信息发送到脊髓，然后从那里信息穿过周围交感神经来收缩皮肤中的血管。通过测量兔耳和大鼠尾巴的皮肤血流量，我们已经能够发现皮肤血管收缩信息到达脊髓的主要大脑路径。这条通路涉及杏仁核和延髓的中缝核团，杏仁核是情绪表达的重要前脑区域。影响心理功能的药物也会影响皮肤的血液流动。摇头丸是一种街头毒品，用来引起快感，也会收缩皮肤血管，可悲的是，体温可能会升高到如此程度，从而导致死亡。摇头丸使兔的皮肤血管强烈收缩，体温升高。摇头丸被认为作用于大脑中含有5-羟色胺的神经细胞，将5-羟色胺(5-HT)释放到特殊的5-HT2A受体上。这些受体的激活既影响心理功能，也影响皮肤血流。用于治疗精神分裂症的现代药物，即所谓的非典型抗精神病药物，如氯氮平和奥氮平，被认为是大脑中5-HT2A受体的拮抗剂。因此，当我们在我们的兔子模型中发现氯氮平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具体的假设。在兔和大鼠身上阐明这些通路将为非典型抗精神病药物的作用机制提供坚实的知识，并很有可能利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。

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.