Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination.

ABSTRACT: The use of cannabis is rapidly expanding worldwide. Thus, innovative studies aimed to identify, understand and potentially reduce cannabis-evoked harms are warranted. Here, we found that Δ⁹-tetrahydrocannabinol, the psychoactive ingredient of cannabis, disrupts autophagy selectively in the striatum, a brain area that controls motor behavior, both in vitro and in vivo. Boosting autophagy, either pharmacologically (with temsirolimus) or by dietary intervention (with trehalose), rescued the Δ⁹-tetrahydrocannabinol-induced impairment of motor coordination in mice. The combination of conditional knockout mouse models and viral vector-mediated autophagy-modulating strategies in vivo showed that cannabinoid CB₁ receptors located on neurons belonging to the direct

SUBMITTER: Blazquez C 

PROVIDER: S-EPMC7417168 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature