Osborne Ashleigh L, Solowij Nadia, Babic Ilijana, Huang Xu-Feng, Weston-Green Katrina
Centre for Translational Neuroscience, School of Medicine, Faculty of Science, Medicine and Health, and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
Centre for Medical and Molecular Biosciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia.
Neuropsychopharmacology. 2017 Jun;42(7):1447-1457. doi: 10.1038/npp.2017.40. Epub 2017 Feb 23.
Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with 10 mg/kg CBD (CONT+CBD, POLY+CBD; n=12 per group) or vehicle (VEH; CONT+VEH, POLY+VEH; n=12 per group) for 3 weeks. Body weight, food and water intake was measured weekly. The Novel Object Recognition and rewarded T-maze alternation tests assessed recognition and working memory, respectively, and the social interaction test assessed sociability. POLY+VEH offspring exhibited impaired recognition and working memory, and reduced social interaction compared to CONT+VEH offspring (p<0.01). CBD treatment significantly improved recognition, working memory and social interaction deficits in the poly I:C model (p<0.01 vs POLY+VEH), did not affect total body weight gain, food or water intake, and had no effect in control animals (all p>0.05). In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection. These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia.
精神分裂症等神经精神疾病与认知障碍有关，包括学习、记忆和注意力缺陷。抗精神病药物在改善认知方面的疗效有限；因此，需要新的治疗药物。大麻二酚（CBD）是大麻的非致幻成分，具有抗炎、神经保护和类抗精神病特性；然而，其改善精神分裂症认知缺陷的能力仍不清楚。我们使用产前感染模型，研究了慢性CBD治疗对认知和社交互动的影响。在妊娠第15天，将同期受孕的Sprague-Dawley孕鼠（n = 16）分为两组，分别给予多聚肌苷酸-多聚胞苷酸（poly I:C）（POLY；4 mg/kg）或生理盐水（CONT）。雄性后代（出生后56天）每天注射两次10 mg/kg CBD（CONT+CBD，POLY+CBD；每组n = 12）或溶剂（VEH；CONT+VEH，POLY+VEH；每组n = 12），持续3周。每周测量体重、食物和水摄入量。新颖物体识别测试和奖励性T迷宫交替测试分别评估识别和工作记忆，社交互动测试评估社交能力。与CONT+VEH后代相比，POLY+VEH后代表现出识别和工作记忆受损，社交互动减少（p<0.01）。CBD治疗显著改善了poly I:C模型中的识别、工作记忆和社交互动缺陷（与POLY+VEH相比，p<0.01），不影响总体重增加、食物或水摄入量，对对照动物也无影响（所有p>0.05）。总之，慢性给予CBD可减轻产前poly I:C感染引起的社交互动和认知缺陷。这些新发现为CBD在治疗精神分裂症认知缺陷和社交退缩方面的潜在应用提供了有趣的启示。
