Acute treatment with cannabinoid receptor agonist WIN55212.2 improves prepulse inhibition in psychosocially stressed mice
Acute treatment with cannabinoid receptor agonist WIN55212.2 improves prepulse inhibition in psychosocially stressed mice
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DOI：
10.1016/j.bbr.2010.11.003
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发表时间：
2011-04-15
影响因子：
2.7
通讯作者：
Havemann-Reinecke, Ursula
中科院分区：
文献类型：
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作者：
Brzozka, Magdalena M.;Fischer, Andre;Havemann-Reinecke, Ursula
大麻，类似于心理社会压力，是众所周知的加剧精神病的经验，并可促成精神病发作的脆弱个体。大麻素受体1 （CB1）在大脑中广泛表达，对调节大麻的作用尤为重要。已知患者长期使用大麻和动物长期使用大麻素会导致脉冲前抑制（PPI）降低。同样，小鼠的慢性社会心理应激也会损害PPI。在本研究中，我们研究了调节cb1受体的物质和慢性社会心理应激对PPI的协同作用。为此，采用“居住者-入侵者”模式将成年C57BI/6J小鼠暴露于慢性社会心理应激环境中。大麻素受体激动剂WIN55212.2作为大麻对大脑影响的替代标记物。暴露于应激后，小鼠被急性注射WIN55212.2 (3 mg/kg)，并与利莫那班（3 mg/kg）（一种特异性cb1受体拮抗剂）预处理或不预处理，并进行行为测试。在PPI测试中，应激小鼠对WIN55212.2的易感性高于对照动物。WIN55212.2对PPI的影响被利莫那班拮抗，提示cb1受体参与感觉运动门控。有趣的是，WIN55212.2增加了心理社会应激小鼠的PPI，尽管先前的大鼠研究显示相反的效果。因此，根据所应用的大麻素/ cb1受体激动剂的剂量和环境条件（社会心理压力），有可能在不同的实验动物中引起相反的效果。综上所述，我们的数据表明，cb1受体可能在大脑中心理社会压力和大麻素的协同作用中发挥关键作用。(C) 2010 Elsevier B.V.版权所有
Cannabis, similar to psychosocial stress, is well known to exacerbate psychotic experiences and can precipitate psychotic episodes in vulnerable individuals. Cannabinoid receptors 1 (CB1) are widely expressed in the brain and are particularly important to mediate the effects of cannabis. Chronic cannabis use in patients and chronic cannabinoids treatment in animals is known to cause reduced prepulse inhibition (PPI). Similarly, chronic psychosocial stress in mice impairs PPI. In the present study, we investigated the synergistic effects of substances modulating the CB1-receptors and chronic psychosocial stress on PPI.For this purpose, adult C57BI/6J mice were exposed to chronic psychosocial stress using the resident-intruder paradigm. The cannabinoid receptor agonist WIN55212.2 served as a surrogate marker for the effects of cannabis in the brain. After exposure to stress mice were acutely injected with WIN55212.2 (3 mg/kg) with or without pre-treatment with Rimonabant (3 mg/kg), a specific CB1-receptor antagonist, and subjected to behavioral testing.Stressed mice displayed a higher vulnerability to WIN55212.2 in the PPI test than control animals. The effects of WIN55212.2 on PPI were antagonized by Rimonabant suggesting an involvement of CB1-receptors in sensorimotor gating. Interestingly, WIN55212.2 increased PPI in psychosocially stressed mice although previous studies in rats showed the opposite effects. It may thus be possible, that depending on the doses of cannabinoids/CB1-receptor agonists applied and environmental conditions (psychosocial stress), opposite effects can be evoked in different experimental animals.Taken together, our data imply that CB1-receptors might play a crucial role in the synergistic effects of psychosocial stress and cannabinoids in brain. (C) 2010 Elsevier B.V. All rights reserved.