Pedrazzi J F C, Issy A C, Gomes F V, Guimarães F S, Del-Bel E A
Departamento de Morfologia, Estomatologia e Patologia Básica, Faculdade de Odontologia, Universidade de São Paulo, Ribeirão Preto, SP, 14049-904, Brasil.
Psychopharmacology (Berl). 2015 Aug;232(16):3057-65. doi: 10.1007/s00213-015-3945-7. Epub 2015 May 6.
The information processing appears to be deficient in schizophrenia. Prepulse inhibition (PPI), which measures the inhibition of a motor response by a weak sensory event, is considered particularly useful to understand the biology of information processing in schizophrenia patients. Drugs that facilitate dopaminergic neurotransmission such as amphetamine induce PPI disruption in human and rodents. Clinical and neurobiological findings suggest that the endocannabinoid system and cannabinoids may be implicated in the pathophysiology and treatment of schizophrenia. Cannabidiol (CBD), a non-psychotomimetic constituent of the Cannabis sativa plant, has also been reported to have potential as an antipsychotic.
Our aim was to investigate if CBD pretreatment was able to prevent PPI disruption induced by amphetamine. Since one possible mechanism of CBD action is the facilitation of endocannabinoid-mediated neurotransmission through anandamide, we tested the effects of an anandamide hydrolysis inhibitor (URB597) in the amphetamine-induced PPI disruption.
Male Swiss mice were treated with CBD systemic or intra-accumbens, or URB597 (systemic) prior to amphetamine and were exposed to PPI test.
Amphetamine (10 mg/kg) disrupted PPI while CBD (15-60 mg/kg) or URB597 (0.1-1 mg/kg) administered alone had no effect. Pretreatment with CBD attenuated the amphetamine-disruptive effects on PPI test after systemic or intra-accumbens administration. Similar effects were also found with the inhibitor of anandamide hydrolysis.
These results corroborate findings indicating that CBD induces antipsychotic-like effects. In addition, they pointed to the nucleus accumbens as a possible site of these effects. The increase of anandamide availability may be enrolled in the CBD effects.
精神分裂症患者的信息处理似乎存在缺陷。前脉冲抑制（PPI）用于测量弱感觉事件对运动反应的抑制作用，被认为对理解精神分裂症患者信息处理的生物学机制特别有用。诸如苯丙胺等促进多巴胺能神经传递的药物会导致人类和啮齿动物的PPI破坏。临床和神经生物学研究结果表明，内源性大麻素系统和大麻素可能与精神分裂症的病理生理学及治疗有关。大麻二酚（CBD）是大麻植物的一种非致幻成分，也被报道具有抗精神病的潜力。
我们的目的是研究CBD预处理是否能够预防苯丙胺诱导的PPI破坏。由于CBD作用的一种可能机制是通过花生四烯乙醇胺促进内源性大麻素介导的神经传递，因此我们测试了花生四烯乙醇胺水解抑制剂（URB597）对苯丙胺诱导的PPI破坏的影响。
雄性瑞士小鼠在给予苯丙胺之前，接受全身或伏隔核内注射CBD，或全身注射URB597，并进行PPI测试。
苯丙胺（10mg/kg）破坏了PPI，而单独给予CBD（15 - 60mg/kg）或URB597（0.1 - 1mg/kg）则没有效果。全身或伏隔核内注射CBD预处理可减轻苯丙胺对PPI测试的破坏作用。花生四烯乙醇胺水解抑制剂也有类似效果。
这些结果证实了表明CBD具有抗精神病样作用的研究发现。此外，它们指出伏隔核可能是这些作用的一个位点。花生四烯乙醇胺可用性的增加可能参与了CBD的作用。
