Department of Pharmacology, School of Medical Sciences and Bosch Institute, University of Sydney, NSW, Australia.
Life Sci. 2010 Oct 23;87(17-18):572-8. doi: 10.1016/j.lfs.2010.09.018. Epub 2010 Sep 25.
Genetic disposition modulates the psychoactive effects of cannabis. Cannabinoids have a greater impact on brain regions that subserve anxiety in Wistar compared to Lewis strain rats. Here we aim to show that this correlates with strain differences in cannabinoid-induced anxiety-related behaviour.
Lewis and Wistar rats were administered vehicle or the synthetic cannabinoid receptor agonist, CP 55,940 (10, 25 and 50μg/kg) before testing in the conditioned ultrasonic vocalization (USV), cat odour avoidance or open area avoidance models.
Animals were placed in a chamber in which they had previously received footshock. Wistar but not Lewis rats re-exposed under the influence of all CP 55,940 doses emitted significantly more USVs than vehicle-treated rats. In the cat odour avoidance model, rats were exposed to cat odour and given the opportunity to hide in a small box. In Wistar but not Lewis rats, 50μg/kg of CP 55,940 magnified hiding behaviour promoted by cat odour exposure. Animals were also tested in the open area avoidance model which occurred in the same arena as the predatory avoidance model but without cat odour. In Wistar, but not Lewis rats, 25 and 50μg/kg of CP 55,940 increased the avoidance of the open space.
CP 55,940 increased anxiety-related behaviour in Wistar rats but not Lewis rats providing a model to dissect the genetic basis of cannabinoid-induced anxiety. We show for the first time that cannabinoids magnify conditioned USVs and cat odour avoidance behaviour dependent on the strain being tested.
遗传倾向调节大麻的精神活性作用。与刘易斯大鼠相比,大麻素对焦虑相关脑区的影响更大。在这里,我们旨在表明,这与大麻素诱导的焦虑相关行为的品系差异相关。
在条件性超声发声(USV)、猫气味回避或开放区域回避模型中,给予刘易斯和 Wistar 大鼠载体或合成大麻素受体激动剂 CP 55,940(10、25 和 50μg/kg)后进行测试。
动物被放置在曾经接受过足部电击的腔室中。在所有 CP 55,940 剂量的影响下,Wistar 但不是 Lewis 大鼠重新暴露时比载体处理的大鼠发出明显更多的 USVs。在猫气味回避模型中,大鼠暴露于猫气味并有机会躲在一个小盒子里。在 Wistar 但不是 Lewis 大鼠中,50μg/kg 的 CP 55,940 放大了猫气味暴露引起的躲藏行为。动物还在开放区域回避模型中进行了测试,该模型与捕食回避模型发生在同一个竞技场中,但没有猫气味。在 Wistar 中,但不是 Lewis 大鼠,CP 55,940 增加了对开放空间的回避。
CP 55,940 增加了 Wistar 大鼠的焦虑相关行为,但没有增加 Lewis 大鼠的焦虑相关行为,为剖析大麻素诱导的焦虑的遗传基础提供了一种模型。我们首次表明,大麻素依赖于正在测试的品系放大条件性 USV 和猫气味回避行为。