TY  - JOUR
PY  - 2020//
TI  - Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination
JO  - Elife
A1  - Blázquez, Cristina
A1  - Ruiz-Calvo, Andrea
A1  - Bajo-Grañeras, Raquel
A1  - Baufreton, Jérôme M.
A1  - Resel, Eva
A1  - Varilh, Marjorie
A1  - Pagano Zottola, Antonio C.
A1  - Mariani, Yamuna
A1  - Cannich, Astrid
A1  - Rodríguez-Navarro, José A.
A1  - Marsicano, Giovanni
A1  - Galve-Roperh, Ismael
A1  - Bellocchio, Luigi
A1  - Guzmán, Manuel
SP  - e56811
EP  - e56811
VL  - 9
IS  - 
N2  - 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 (striatonigral) pathway are required for the motor-impairing activity of Δ9-tetrahydrocannabinol by inhibiting local autophagy. Taken together, these findings identify inhibition of autophagy as an unprecedented mechanistic link between cannabinoids and motor performance, and suggest that activators of autophagy might be considered as potential therapeutic tools to treat specific cannabinoid-evoked behavioral alterations.<p />  <p>Language: en</p>
LA  - en
SN  - 2050-084X
UR  - http://dx.doi.org/10.7554/eLife.56811
ID  - ref1
ER  -