Repeated exposure to JWH‐018 induces adaptive changes in the mesolimbic and mesocortical dopaminergic pathways, glial cells alterations, and behavioural correlates

Abstract Background and Purpose: Spice/K2 herbal mixtures, containing synthetic cannabinoids such as JWH‐018, have been marketed as marijuana surrogates since 2004. JWH‐018 has cannabinoid CB1 receptor‐dependent reinforcing properties and acutely increases dopaminergic transmission selectively in the NAc shell. Here, we tested the hypothesis that repeated administration of JWH‐018 (i) modulates behaviour, (ii) affects dopaminergic transmission and its responsiveness to motivational stimuli, and (iii) is associated with a neuroinflammatory phenotype. Experimental Approach: Rats were administered with JWH‐018 once a day for