The establishment of animal model for negative syndrome of schizophrenia and its pharmacological annlication

精神分裂症阴性综合征动物模型的建立及其药理作用

• 批准号: 07672462
• 负责人: YAMAMOTO Tsuneyuki
• 金额: $ 1.47万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672462/
• 关键词: Schizophrenia; Negative syndrome model; DELTA^9-Tetrahydrocannabinol; Phencyclidene; Attentional performance; Delayd matching-to-sample task; Fos protein; Behavioral sensitization; Λ^9tetrahydrocannabinol; 注意機能障害; Fosタンパク; 選択反応時間課題; 大麻; cocai

This research is fundamental studies for establishing animal model for negative syndrome of schizophrenia, using DELTA^9-tetrahydrocannabinol (THC) and phencyclidine (PCP) which produce similar behavioral changes of negative syndrome in schizophrenic patients.1.The effect of repeated administration of THC at a dose of 10 mg/kg (once a day for 4 days) 24 hr after administration on delayd matching-to-sample (DMTS) performance in rats using a 3-lever operant apparatus was examined. Although DMTS performance was not changed on the 1st day, it was impaired on the 2nd day. The impairment was potentiated in dependence of repeated administration. After withdrawal of THC,the impairment of DMTS performance gradually disappeared readministration of 10 mg/kg THC resulted in marked impairment of DMTS performance at 24 hr after administration ; behavioral sensitization developed. Furthermore, the suppressive state of lever-pressing induced by repeated THC administration may be a useful animal model … More for amotivational syndrome, similar to negative syndrome in schizoprenic patients.2.We examined whether administration of THC induces the expression of Fos protein or not in the rat brain. Administration of 10 mg/kg THC produced a significant increase in Fos-immunoreactive cells in the striatum and the nucleus accumbens. However, in the globus pallidus, hippocampus and substantia nigra pars reticula, there were few or no Fos-immunoreactive cells induced by THC.SCH-23390, a selective dopamine D_1 receptor antagonist, but not sulpiride, a selective dopamine D_2 receptor antagonist, produced a significant block of the effects of THC on Fos expression in the striatum and the nucleus accumbens. These findings indicate that THC induces the expression of Fos protein and that this expression is mediated at least by dopamine D_1 receptors.3.Attentional and information processing abnormalities have been noted frequently in schizophrenia. We examined the influence of PCP on attentional performance using a 3-choice serial reaction time task in rats. PCP was found to produce an attention deficit, as indicated by a delayd choice reaction time and a reduced choice accuracy. Sigma antagonists (NE-100, DuP734 and XJ448) blocked the attention deficit elicited by PCP.Judging from these results, it is concluded that this process may be mediated by sigma receptors. Less

本研究为建立精神分裂症阴性症状动物模型奠定了基础，使用Δ ^9-四氢大麻酚（THC）和苯环己哌啶（PCP）在精神分裂症患者中产生类似阴性综合征的行为改变。1.以10 mg/kg剂量重复施用THC的影响（每天一次，持续4天）给药后24小时，使用3杠杆操作装置检查大鼠的延迟样品匹配（DMTS）性能。虽然DMTS性能在第1天没有改变，但在第2天受损。这种损害依赖于重复给药而增强。停药后，DMTS表现的损害逐渐消失，再给药10 mg/kg THC，24 h后DMTS表现明显损害，出现行为敏感化。此外，反复给予THC诱导的细胞内压抑制状态可能是有用的动物模型 ...更多信息 2.我们检测了THC是否诱导大鼠脑内Fos蛋白的表达。给药10毫克/公斤四氢大麻酚产生了显着增加的Fos免疫反应细胞在纹状体和丘脑核。多巴胺D_1受体拮抗剂SCH-23390可阻断THC对纹状体和中脑核Fos表达的影响，而多巴胺D_2受体拮抗剂舒必利则不能阻断THC对纹状体和中脑核Fos表达的影响。提示THC可诱导Fos蛋白的表达，并且这种表达至少是通过多巴胺D_1受体介导的。3.注意和信息加工异常在精神分裂症中较为常见。我们研究了PCP对大鼠注意表现的影响，采用3选择系列反应时任务。PCP被发现产生注意力缺陷，如延迟的选择反应时间和减少的选择准确性所示。Sigma受体拮抗剂NE-100、DuP 734和XJ 448可阻断PCP引起的注意障碍，提示这一过程可能是由Sigma受体介导的。少

项目成果

A.Miyamoto: "Effect of repeated administration of Δ^9-tetrahydrocannabinol on delayed matching-to-sample perfomance in rats" Neuroscience Letters. 201. 139-142 (1995)

A. Miyamoto：“重复施用 Δ^9-四氢大麻酚对大鼠延迟匹配样本性能的影响”《神经科学快报》201. 139-142 (1995)。

A.Miyamoto: "Roles of dopamine D_1 receptors in Δ^9-tetrahydrocannabinol-induced expression of Fos protein in the rat brain" Brain Research. 710. 234-240 (1996)

A.Miyamoto：“多巴胺 D_1 受体在 Δ^9-四氢大麻酚诱导的大鼠大脑 Fos 蛋白表达中的作用”《大脑研究》710. 234-240 (1996)。

山本経之: "生物学的精神医学 Vol.10不安とうつの生物学" 学会出版センター, 187 (1995)

山本常之：《生物精神病学 Vol.10 焦虑和抑郁的生物学》学会出版中心，187（1995）

Miyamoto, A. et al.: "Effect of repeated administration of Δ^9-tetrahydrocannabinol on delayed matching-to-sample performance in rats." Neurosci. Lett.201. 139-142 (1995)

Miyamoto, A. 等人：“重复施用 Δ^9-四氢大麻酚对大鼠样本匹配延迟的影响。Neurosci。139-142 (1995)”

山本経之: "学習・記憶障害と神経伝達物質異常" Molecular Medicine. 32. 146-153 (1995)

Tsuneyuki Yamamoto：“学习/记忆障碍和神经递质异常”分子医学。32。146-153（1995）