Cannabinoid-induced motor dysfunction via autophagy inhibition



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Blázquez Ortiz, Cristina and Ruiz Calvo, Andrea and Bajo Grañeras, Raquel and Baufreton, Jérôme M. and Resel, Eva and Varilh, Marjorie and Pagano Zottola, Antonio C. and Mariani, Yamuna and Cannich, Astrid and Rodríguez Navarro, José A. and Marsicano, Giovanni and Galve Roperh, Ismael and Bellocchio, Luigi and Guzmán Pastor, Manuel (2020) Cannabinoid-induced motor dysfunction via autophagy inhibition. Autophagy, 16 (12). pp. 2289-2291. ISSN 1554-8635

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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/CB1R (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 Δ9-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.

Item Type:Article
Uncontrolled Keywords:Autophagy; Cannabinoid; Drug abuse; Motor behavior; MTOR; Striatum
Subjects:Medical sciences > Medicine > Alternative medicine
Medical sciences > Medicine > Neurosciences
ID Code:64940
Deposited On:20 Apr 2021 06:58
Last Modified:14 Jan 2022 12:25

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