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

1胜9负。我们研究了sigma受体相关药物对小鼠条件恐惧应激（CFS）反应的影响，这种反应不能被典型的抗抑郁药和抗焦虑药所减弱。与中边缘多巴胺能系统密切相关的苯妥英敏感的sigma1受体的激活被证明参与了(+)-SKF-10,047和右美沙芬，sigma1受体激动剂对CFS反应的改善作用。脱氢表雄酮硫酸（DHEAS）和孕烯醇酮硫酸，神经类固醇有亲和力的sigma1受体，也减轻CFS反应。CFS反应小鼠血清中DHEAS浓度低于非应激小鼠。这些发现提示神经类固醇在CFS反应的表达中起重要作用。我们利用苯环利定（phencyclidine， POP）在人体内产生精神分裂症样症状，建立了精神分裂症阴性症状动物模型，并考察了sigma受体相关药物对pcp诱导的阴性症状样作用的影响。（+） - skf - 10047和PCP在小鼠中诱导阴性症状样作用。西格玛受体拮抗剂不能减弱pcp诱导的阴性症状样作用。虽然西格玛受体可能参与了pcp诱导的阴性症状样行为的表达，但西格玛受体拮抗剂不太可能是精神分裂症阴性症状潜在治疗药物的候选药物。采用药物鉴别试验研究了sigma受体相关药物对大鼠PCP鉴别刺激效应的影响。Sigma受体激动剂在训练大鼠区分PCP和生理盐水时没有产生PCP样的区分刺激作用。西格玛受体拮抗剂不减弱PCP的鉴别刺激作用。这些结果表明，西格玛受体不参与pcp的鉴别刺激作用。一氧化氮合酶抑制剂N^ g -硝基- l -精氨酸和非竞争性NMDA受体拮抗剂二唑西平分别对小鼠和大鼠的空间工作记忆造成损伤。（+） - skf - 10047可改善这些损伤，NE-lO0可拮抗这种改善作用。这些发现表明，sigma受体参与了空间记忆形成所需过程的调节。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