Calpe-López Claudia, Gasparyan Ani, Navarrete Francisco, Manzanares Jorge, Miñarro Jose, Aguilar Maria A
Unit of Research 'Neurobehavioural mechanisms and endophenotypes of addictive behaviour', Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain.
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain.
J Psychopharmacol. 2021 Jul;35(7):864-874. doi: 10.1177/0269881120965952. Epub 2021 Jan 9.
Cocaine dependence is an important problem without any effective pharmacological treatment. Some preclinical studies have suggested that cannabidiol (CBD), a component of the plant, could be useful for the treatment of cocaine use disorders.
This work aims to evaluate the ability of CBD to reduce priming- and stress-induced reinstatement of the conditioned place preference (CPP) induced by cocaine.
Young adult CD-1 male mice were allocated to 10 groups ( = 12/group), conditioned with cocaine (10 mg/kg) and exposed to extinction of CPP (two sessions per week). When extinction was achieved, each group received the corresponding treatment before the reinstatement test. In experiment 1, six groups were used: vehicle+saline (Veh+Sal), 5 mg/kg cocaine alone (Veh+Coc) or with CBD 30 or 60 mg/kg (CBD30+Coc, CBD60+Coc) and CBD alone (CBD30+Sal, CBD60+Sal). In experiment 2, four groups were used: exploration (Veh+Expl), social defeat (Veh+SD) and social defeat with CBD (CBD30+SD and CBD60+SD). Furthermore, the relative gene expression of the dopamine transporter (DAT) in the ventral tegmental area was measured.
All mice acquired cocaine CPP and extinguished it after three or four weeks. Only the groups treated with cocaine priming (Veh+Coc) or exposed to social defeat (Veh+SD) showed reinstatement of CPP. Interestingly, CBD itself did not induce reinstatement and blocked the reinstating effects of cocaine priming and social defeat. Furthermore, cocaine priming increased DAT gene expression in the ventral tegmental area and CBD completely reversed this effect.
These results suggest that CBD could reduce reinstatement to cocaine seeking after a period of abstinence.
可卡因成瘾是一个重要问题,目前尚无有效的药物治疗方法。一些临床前研究表明,大麻二酚(CBD)作为该植物的一种成分,可能对治疗可卡因使用障碍有用。
本研究旨在评估CBD减少可卡因诱导的条件性位置偏爱(CPP)的启动和应激诱导复吸的能力。
将成年雄性CD-1小鼠分为10组(每组n = 12),用可卡因(10 mg/kg)进行条件化处理,并使其暴露于CPP消退阶段(每周两次)。当达到消退标准后,每组在复吸测试前接受相应处理。在实验1中,使用6组:溶剂+生理盐水(Veh+Sal)、单独使用5 mg/kg可卡因(Veh+Coc)或与30或60 mg/kg CBD联合使用(CBD30+Coc、CBD60+Coc)以及单独使用CBD(CBD30+Sal、CBD60+Sal)。在实验2中,使用4组:探索组(Veh+Expl)、社会挫败组(Veh+SD)以及社会挫败+CBD组(CBD30+SD和CBD60+SD)。此外,还测量了腹侧被盖区多巴胺转运体(DAT)的相对基因表达。
所有小鼠均获得可卡因CPP,并在三到四周后消退。只有接受可卡因启动处理的组(Veh+Coc)或经历社会挫败的组(Veh+SD)表现出CPP复吸。有趣的是,CBD本身不会诱导复吸,并且能阻断可卡因启动和社会挫败的复吸效应。此外,可卡因启动增加了腹侧被盖区DAT基因表达,而CBD完全逆转了这种效应。
这些结果表明,CBD可减少戒断一段时间后对可卡因寻求行为的复吸。