Cannabidiol prevents priming- and stress-induced reinstatement of the conditioned place preference induced by cocaine in mice

Background: Cocaine dependence is an important problem without any effective pharmacological treatment. Some preclinical studies have suggested that cannabidiol (CBD), a component of the Cannabis sativa plant, could be useful for the treatment of cocaine use disorders. Aims: 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. Methods: Young adult CD-1 male mice were allocated to 10 groups (n = 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. Results: 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. Conclusion: These results suggest that CBD could reduce reinstatement to cocaine seeking after a period of abstinence.