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大麻二酚可减轻 MK-801 诱导的小鼠被动回避测试中精神分裂症的认知症状。

Cannabidiol Attenuates MK-801-Induced Cognitive Symptoms of Schizophrenia in the Passive Avoidance Test in Mice.

机构信息

Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4a Chodzki Str., 20-093 Lublin, Poland.

出版信息

Molecules. 2021 Oct 2;26(19):5977. doi: 10.3390/molecules26195977.

Abstract

Schizophrenia is a chronic mental disorder that disturbs feelings and behavior. The symptoms of schizophrenia fall into three categories: positive, negative, and cognitive. Cognitive symptoms are characterized by memory loss or attentional deficits, and are especially difficult to treat. Thus, there is intense research into the development of new treatments for schizophrenia-related responses. One of the possible strategies is connected with cannabidiol (CBD), a cannabinoid compound. This research focuses on the role of CBD in different stages of memory (acquisition, consolidation, retrieval) connected with fear conditioning in the passive avoidance (PA) learning task in mice, as well as in the memory impairment typical of cognitive symptoms of schizophrenia. Memory impairment was provoked by an acute injection of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (animal model of schizophrenia). Our results revealed that an acute injection of CBD (30 mg/kg; intraperitoneally (i.p.) improved all phases of long-term fear memory in the PA test in mice. Moreover, the acute injection of non-effective doses of CBD (1 or 5 mg/kg; i.p.) attenuated the memory impairment provoked by MK-801 (0.6 mg/kg; i.p.) in the consolidation and retrieval stages of fear memory, but not in the acquisition of memory. The present findings confirm that CBD has a positive influence on memory and learning processes in mice, and reveals that this cannabinoid compound is able to attenuate memory impairment connected with hypofunction of glutamate transmission in a murine model of schizophrenia.

摘要

精神分裂症是一种慢性精神障碍,会扰乱情感和行为。精神分裂症的症状分为三类:阳性、阴性和认知。认知症状的特征是记忆力减退或注意力缺陷,且尤其难以治疗。因此,人们正在深入研究开发针对精神分裂症相关反应的新疗法。其中一种可能的策略与大麻二酚(CBD)有关,它是一种大麻素化合物。这项研究主要关注 CBD 在与恐惧条件反射相关的记忆(获得、巩固、检索)不同阶段的作用,以及在精神分裂症认知症状中常见的记忆障碍。记忆障碍是通过急性注射 N-甲基-D-天冬氨酸(NMDA)受体拮抗剂 MK-801(精神分裂症动物模型)来引发的。我们的研究结果表明,急性注射 CBD(30mg/kg;腹腔内注射)可改善 PA 测试中小鼠的长期恐惧记忆的所有阶段。此外,急性注射非有效剂量的 CBD(1 或 5mg/kg;腹腔内注射)可减轻 MK-801(0.6mg/kg;腹腔内注射)在恐惧记忆的巩固和检索阶段引起的记忆障碍,但不能减轻记忆获得阶段的障碍。本研究结果证实 CBD 对小鼠的记忆和学习过程有积极影响,并表明这种大麻素化合物能够减轻谷氨酸传递功能低下与精神分裂症小鼠模型相关的记忆障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df77/8513030/52574378125f/molecules-26-05977-g001.jpg

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