Cannabinoid-induced motor dysfunction via autophagy inhibition. Issue 12 (1st December 2020)

• Record Type: Journal Article
• Authors: Blázquez, Cristina; Ruiz-Calvo, Andrea; Bajo-Grañeras, Raquel; Baufreton, Jerome 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, Manuel
• Is Part Of: Autophagy. Volume 16:Issue 12(2020)
• Page Start: 2289
• Page End: 2291
• Publication Date: 2020-12-01
• Subjects: Autophagy -- cannabinoid -- drug abuse -- motor behavior -- MTOR -- striatum; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2020.1827560
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: The recreational and medical use of cannabis is largely increasing worldwide. Cannabis use, however, can cause adverse side effects, so conducting innovative studies aimed to understand and potentially reduce cannabis-evoked harms is important. Previous research conducted on cultured neural cells had supported that CNR1/CB1 R (cannabinoid receptor 1), the main molecular target of cannabis, affects macroautophagy/autophagy. However, it was not known whether CNR1 controls autophagy in the brain in vivo, and, eventually, what the functional consequences of a potential CNR1-autophagy connection could be. We have now found that Δ 9 -tetrahydrocannabinol (THC), the major intoxicating constituent of cannabis, impairs autophagy in the mouse striatum. Administration of autophagy activators (specifically, the rapalog temsirolimus and the disaccharide trehalose) rescues THC-induced autophagy inhibition and motor dyscoordination. The combination of various genetic strategies in vivo supports the idea that CNR1 molecules located on neurons belonging to the direct (striatonigral) pathway are required for the autophagy- and motor-impairing activity of THC. By identifying autophagy as a mechanistic link between THC and motor performance, our findings may open a new conceptual view on how cannabis acts in the brain.