Role of sigma receptors in the animal models for neuropsychological diseases.

9比1。我们研究了Sigma受体相关药物对小鼠条件性恐惧应激(CFS)反应的影响，这种反应不能被典型的抗抑郁药物和抗焦虑药物减弱。与中脑边缘多巴胺能系统密切联系的苯妥英敏感的Sigma1受体的激活被证实参与了()-SKF-10,047和右美沙芬，Sigma1受体激动剂改善CFS反应的作用。脱氢表雄酮硫酸盐(DHEAS)和孕烯醇酮硫酸盐，这两种与Sigma1受体有亲和力的神经类固醇，也可以减弱CFS的反应。CFS反应小鼠血清中DHEAS浓度低于非应激小鼠。这些发现表明，神经类固醇在CFS反应的表达中起着重要作用。我们利用苯环利定(POP)建立了精神分裂症阴性症状动物模型，并检测了…的作用。S等更多的西格玛受体相关药物对五氯苯酚所致的阴性症状样作用。()-SKF-10,047和PCP对小鼠的阴性症状样作用。Sigma受体拮抗剂不能减弱PCP诱导的阴性症状样作用。虽然Sigma受体可能参与PCP诱导的阴性症状样作用的表达，但Sigma受体拮抗剂不太可能成为治疗精神分裂症阴性症状的潜在治疗药物。我们用药物辨别实验检测了西格玛受体相关药物对五氯苯酚辨别刺激效应的影响。Sigma受体激动剂在被训练来区分PCP和生理盐水的大鼠中不产生PCP样的区别刺激效应。Sigma受体拮抗剂不能减弱PCP的辨别刺激效应。这些发现表明，Sigma受体不参与PCP.9-4的辨别性刺激效应。一氧化氮合酶抑制剂N-硝基-L-精氨酸和非竞争性N-甲基-D-甲基-D-天冬氨酸受体拮抗剂地佐西平分别损害小鼠和大鼠的空间工作记忆。这些损伤可被()-SKF-10,047所改善，这种改善作用被NE-10所拮抗。这些发现表明，Sigma受体参与了空间记忆形成所需的过程的调节。较少

9-1. We examined the effects of sigma receptor-related agents on conditioned fear stress (CFS) response that could not be attenuated by typical antidepressants and anxiolytics in mice. The activation of phenytoin-sensitive sigma1 receptors which are closely connected to the meso-limbic dopaminergic systems was demonstrated to be involved in the ameliorating effects of (+) -SKF-10,047 and dextromethorphan, sigma1 receptor agonists on the CFS response. Dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate, neurosteroids that have an affinity for sigma1 receptors, also attenuated the CFS response. The DHEAS concentration in the serum of mice showing CFS response was lower than that in the non-stressed mice. These findings suggested that neurosteroids play an important role in the expression of CFS response.9-2. We developed the animal model for negative symptom in schizophrenia using phencyclidine (POP), which produces schizophrenic-like symptom in human, and examined the effect … More s of sigma receptor-related agents on PCP-induced negative symptom-like action. (+) -SKF-10,047 as well as PCP induced negative symptom-like action in mice. Sigma receptor antagonists did not attenuate the PCP-induced negative symptom-like action. Although sigma receptors may be involved in expression of PCP-induced negative symptom-like action, it is unlikely that sigma receptor antagonists are candidates of potential therapeutic drug for negative symptoms in schizophrenia.9-3. We examined the effects of sigma receptor-related agents on the discriminative stimulus effects of PCP in rats using drug discrimination test. Sigma receptor agonists did not produce PCP-like discriminative stimulus effects in rats trained to discriminate PCP from saline. The discriminative stimulus effects of PCP were not attenuated by sigma receptor antagonists. These findings suggested that sigma receptors were not involved in the discriminative stimulus effects of PCP.9-4. N^G-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor and dizocilpine, non-competitive NMDA receptor antagonist, impaired the spatial working memory in mice and rats, respectively. These impairments were ameliorated by (+) -SKF-10,047, the ameliorating effect being antagonized by NE-lO0. These findings suggested that sigma receptors were involved in the regulation of processes required for spatial memory formation. Less