Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: Possible involvement of 5HT1A receptors
Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: Possible involvement of 5HT1A receptors
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DOI：
10.1016/j.jpsychires.2012.08.012
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发表时间：
2012-11-01
影响因子：
4.8
通讯作者：
Guimaraes, Francisco Silveira
中科院分区：
文献类型：
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作者：
Campos, Alline Cristina;Ferreira, Frederico Rogerio;Guimaraes, Francisco Silveira
创伤后应激障碍(PTSD)是一种伴随着创伤经历而导致的丧失能力的综合征。捕食者的暴露促进了啮齿动物的长期焦虑效应，这种效应与创伤后应激障碍患者的症状有关。大麻二酚(CBD)是大麻中的一种非精神分裂症成分，具有抗焦虑作用。本研究在创伤后应激障碍模型上研究了CBD的抗焦虑作用。雄性Wistar大鼠暴露于捕食者(猫)1h后，单次或重复ip。车辆或CBD的管理。应激7天后，动物接受高架+迷宫实验。为探讨5HT1a受体在CBD效应中的作用，动物用5HT1a受体拮抗剂WAY100635进行预处理。为了探讨这些效应的可能神经生物学机制，我们检测了5HT1A受体在海马区、额叶皮质、杏仁复合体和中脑导水管周围灰质背侧的表达。重复给予CBD可阻止单一捕食者暴露所促进的长期焦虑效应。WAY100635可减弱CBD的作用。捕食者暴露7天后，5HT1AmRNA在额叶皮质和海马区表达上调。CBD和帕罗西汀未能阻止这种作用。脑源性神经营养因子的表达无明显变化。总而言之，捕食者暴露促进了海马区和额叶皮质5HT1a受体基因表达的长期上调。反复给予CBD可阻止捕食者暴露后观察到的长期焦虑效应，可能是通过促进5HT1A受体的神经传递。我们的结果表明，CBD具有治疗创伤后应激障碍的有益潜力，5HT1A受体可能是治疗这种疾病的靶点。(C)2012爱思唯尔有限公司。保留所有权利。
Posttraumatic stress disorder (PTSD) is an incapacitating syndrome that follows a traumatic experience. Predator exposure promotes long-lasting anxiogenic effect in rodents, an effect related to symptoms found in PTSD patients. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa with anxiolytic effects. The present study investigated the anti-anxiety actions of CBD administration in a model of PTSD. Male Wistar rats exposed to a predator (cat) received, 1 h later, singled or repeated i.p. administration of vehicle or CBD. Seven days after the stress animals were submitted to the elevated plus maze. To investigate the involvement of 5HT1A receptors in CBD effects animals were pre-treated with WAY100635, a 5HT1A receptor antagonist. To explore possible neurobiological mechanisms involved in these effects, 5HT1A receptor mRNA and BDNF protein expression were measured in the hippocampus, frontal cortex, amygdaloid complex and dorsal periaqueductal gray. Repeated administration of CBD prevented long-lasting anxiogenic effects promoted by a single predator exposure. Pretreatment with WAY100635 attenuated CBD effects. Seven days after predator exposure 5HT1A mRNA expression was up regulated in the frontal cortex and hippocampus. CBD and paroxetine failed to prevent this effect. No change in BDNF expression was found. In conclusion, predator exposure promotes long-lasting up-regulation of 5HT1A receptor gene expression in the hippocampus and frontal cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5HT1A receptors neurotransmission. Our results suggest that CBD has beneficial potential for PTSD treatment and that 5HT1A receptors could be a therapeutic target in this disorder. (C) 2012 Elsevier Ltd. All rights reserved.