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



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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) Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination. eLife, 9 (e56811). pp. 1-24. ISSN Electronic: 2050-084X

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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.

Item Type:Article
Uncontrolled Keywords:Autophagy; Cannabinoid; Drug abuse; mTOR; Motor behaviour; Mouse; Neuroscience; Striatum
Subjects:Medical sciences > Biology > Biochemistry
Medical sciences > Biology > Neurosciences
ID Code:64568
Deposited On:23 Mar 2021 09:00
Last Modified:23 Mar 2021 09:28

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