Costa-Campos L, Dassoler S C, Rigo A P, Iwu M, Elisabetsky E
Curso de Pós-graduação em Ciências Biológicas-Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos 2600/anexo, Porto Alegre, RS, Brazil.
Pharmacol Biochem Behav. 2004 Mar;77(3):481-9. doi: 10.1016/j.pbb.2003.12.002.
Anxiolytic properties may be a crucial feature of newer antipsychotics associated with the improvement of negative symptoms in schizophrenic patients. The indole alkaloid alstonine acts as an atypical antipsychotic in behavioral models, but differs in its dopamine and serotonin binding profile. The purpose of this study was to verify if alstonine possesses anxiolytic properties in mice. The hole-board and light/dark models were used; moreover, the participation of D(1), 5-HT(2), NMDA and gamma-aminobutyric acid (GABA) receptors was likewise investigated. Alstonine clearly behaves as anxiolytic in both hole-board and light/dark situations. Pretreatment with the 5-HT(2A/2C) serotonin receptor antagonist ritanserin reverted the effects of alstonine in both the hole-board and light/dark models, suggesting the involvement of these receptors in the alstonine mechanism of action. The involvement of glutamate NMDA receptors should also be considered, given that alstonine partially reversed the increase in locomotion induced by MK-801 in the hole board, as well as MK-801-induced hyperlocomotion in motor activity apparatus.
抗焦虑特性可能是新型抗精神病药物的一个关键特征，与精神分裂症患者阴性症状的改善有关。吲哚生物碱阿斯托宁在行为模型中表现为非典型抗精神病药物，但其多巴胺和5-羟色胺结合谱有所不同。本研究的目的是验证阿斯托宁在小鼠中是否具有抗焦虑特性。使用了洞板和明暗模型；此外，还研究了D(1)、5-HT(2)、N-甲基-D-天冬氨酸（NMDA）和γ-氨基丁酸（GABA）受体的参与情况。阿斯托宁在洞板和明暗两种情况下均明显表现出抗焦虑作用。用5-HT(2A/2C) 5-羟色胺受体拮抗剂利坦色林预处理可逆转阿斯托宁在洞板和明暗模型中的作用，表明这些受体参与了阿斯托宁的作用机制。鉴于阿斯托宁部分逆转了MK-801在洞板中诱导的运动增加以及在运动活动装置中MK-801诱导的运动亢进，谷氨酸NMDA受体的参与也应予以考虑。
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