Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Behav Brain Res. 2011 Sep 23;222(2):299-308. doi: 10.1016/j.bbr.2011.03.053. Epub 2011 Mar 31.
Cannabidiol is a non-psychoactive phytocannabinoid which, based on several previous preclinical and clinical reports, is purported to have antipsychotic potential. The purpose of this investigation was to further investigate if these effects would be seen using an MK-801-induced rat model of aspects of schizophrenia. MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviours which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia. Following a 4-day acclimatisation to the holding room, rats were acclimatised to startle chambers on day 5 and their prepulse inhibition (PPI) determined on day 6 following treatment with cannabidiol or vehicle and MK-801 or vehicle. On day 9, rats were acclimatised to the social interaction testing arena and on day 10, were tested for social interaction and locomotor activity following the same treatments. Cannabidiol treatment alone disrupted PPI and produced hyperactivity but had no effect on social behaviour. Cannabidiol had no effect on MK-801-induced disruption of PPI or hyperactivity but showed potential towards inhibiting MK-801-induced social withdrawal. As a comparator, we also tested the effect of the atypical antipsychotic clozapine which only partially reversed MK-801-induced disruption of PPI but was able to reverse MK-801-induced hyperactivity and social withdrawal. In conclusion, cannabidiol showed both propsychotic activity and partial antipsychotic activity in an MK-801-induced model of aspects of schizophrenia. Further behavioural studies would be required using a range of species, strains, animal models and testing paradigms to conclusively establish the antipsychotic potential of cannabidiol.
大麻二酚是一种非精神活性的植物大麻素，基于几项先前的临床前和临床报告，据称它具有抗精神病的潜力。本研究的目的是进一步研究这些效应是否会在使用 MK-801 诱导的精神分裂症模型中出现。MK-801 是一种 NMDA 受体拮抗剂，已知会产生过度活跃、前脉冲抑制和社交回避缺陷，这些行为与精神分裂症的一些阳性、认知和阴性症状非常相关。在适应 4 天后适应饲养室后，第 5 天适应惊吓室，并在大麻二酚或载体和 MK-801 或载体处理后第 6 天测定前脉冲抑制（PPI）。第 9 天，大鼠适应社交互动测试竞技场，第 10 天，在相同的治疗后，测试社交互动和运动活动。大麻二酚单独治疗会破坏 PPI 并产生过度活跃，但对社交行为没有影响。大麻二酚对 MK-801 诱导的 PPI 破坏或过度活跃没有影响，但显示出抑制 MK-801 诱导的社交回避的潜力。作为对照，我们还测试了非典型抗精神病药氯氮平的效果，氯氮平仅部分逆转了 MK-801 诱导的 PPI 破坏，但能够逆转 MK-801 诱导的过度活跃和社交回避。总之，大麻二酚在 MK-801 诱导的精神分裂症模型中表现出既具有促精神病作用又具有部分抗精神病作用。需要使用一系列物种、品系、动物模型和测试范式进行进一步的行为研究，以明确确定大麻二酚的抗精神病潜力。
