2026-06-26T10:42:01Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/79412024-06-24T17:53:15Zcom_20.500.14352_14col_20.500.14352_15

Blázquez Ortiz, Cristina Ruiz-Calvo, Andrea Bajo Grañeras, Raquel Baufreton, Jérôme M. Resel, Eva Varilh, Marjorie Pagano Zottola, Antonio C. Mariani, Yamuna Cannich, Astrid Rodríguez-Navarro, José A. Marsicano, Giovanni Galve Roperh, Ismael Bellocchio, Luigi Guzmán Pastor, Manuel 2023-06-17T09:01:09Z 2023-06-17T09:01:09Z 2020-08-10 Electronic: 2050-084X 10.7554/eLife.56811 https://hdl.handle.net/20.500.14352/7941 https://elifesciences.org/articles/56811 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 D 9 -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 D 9 -tetrahydrocannabinol-induced impairment of motor coordination in mice. The combination of conditional knockout mouse models and viral vector-mediated autophagymodulating 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 D 9 - 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. eng https://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination journal article