Risperidone attenuates MK-801-induced hyperlocomotion in mice via the blockade of serotonin 5-HT2A/2C receptors
Risperidone attenuates MK-801-induced hyperlocomotion in mice via the blockade of serotonin 5-HT2A/2C receptors
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DOI：
10.1016/j.ejphar.2007.02.031
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发表时间：
2007-06-14
影响因子：
5
通讯作者：
Liang, Jian-Hui
中科院分区：
文献类型：
--
作者：
Su, Yun-Ai;Si, Tian-Mei;Liang, Jian-Hui
谷氨酸 N-甲基-D-天冬氨酸 (NMDA) 受体拮抗剂，如苯环己哌啶 (PCP)，会在人类中引起类似精神分裂症的症状，并在动物中引起行为异常，例如多动症。我们研究了非典型抗精神病药利培酮对 NMDA 受体拮抗剂 5,R,10S-(+)-5-methyl-10,11-diHydro-5H-二苯并[a,d]-环庚烯-5,10-亚胺马来酸氢 (MK-801)（一种 NMDA 受体拮抗剂）产生的过度运动的影响。 MK-801（0.125、0.25、0.50 mg/kg）剂量依赖性地增加了小鼠在 90 分钟内在开放区域中移动的总距离。 MK-801 (0.25 mg/kg) 引起的总行进距离的增加通过利培酮预处理而减弱，该剂量单独使用对自发运动活动没有影响。此外，(+/-)-1-(2, 5-二甲氧基-4-碘苯基)-2-氨基丙烷盐酸盐 (DOI)（一种血清素 5-HT2A/2C 受体激动剂）在无法改变 MK-801 诱导的自发运动活性或过度运动的剂量下，逆转了利培酮的减弱作用。 5-羟色胺 5-HT2A/2c 受体拮抗剂利坦色林增强了利培酮的抑制作用。这些发现表明，利培酮通过阻断 5-羟色胺 5-HT2A/2c 受体来减弱 MK-801 诱导的小鼠过度运动。 (c) 2007 Elsevier B.V 保留所有权利。
Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists, like phencyclidine (PCP), elicit schizophrenia-like symptoms in humans and behavioral abnormalities in animals, such as hyperactivity. We investigated the effect of the atypical antipsychotic risperidone on hyperlocomotion produced in mice by 5,R,10S-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK-801), an NMDA receptor antagonist. MK-801 (0.125, 0.25, 0.50 mg/kg) dose-dependently increased the total distance traveled in an open field during a 90 min period in mice. The increase in MK-801 (0.25 mg/kg)-induced total distance traveled was attenuated by pretreatment with risperidone at doses that alone had no effect on spontaneous locomotor activity. Furthermore, (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), a serotonin 5-HT2A/2C receptor agonist, at the doses that failed to change spontaneous locomotor activity or hyperlocomotion induced by MK-801, reversed the attenuation by risperidone. The serotonin 5-HT2A/2c receptor antagonist, ritanserin, enhanced the inhibitory effect of risperidone. These findings indicate that risperidone attenuates MK-801-induced hyperlocomotion in mice by blocking serotonin 5-HT2A/2c receptors. (c) 2007 Elsevier B.V All rights reserved.