Cannabidiol has a unique effect on global brain activity: a pharmacological, functional MRI study in awake mice

Journal of Translational Medicine

Praveen Kulkarni¹  Aymen H. Sadaka¹  Ana G. Ozuna¹  Craig F. Ferris²  Bruce S. Cushing³  Richard J. Ortiz³  Heather B. Bradshaw⁴  Clare T. Johnson⁴  Ai-Ling Li⁴  Andrea G. Hohmann⁵ 

[1] Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA;Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA;Psychology and Pharmaceutical Sciences, Northeastern University, Boston, MA, USA;Department of Psychology, Northeastern University, 125 NI Hall, 360 Huntington Ave, 02115-5000, Boston, MA, USA;Department of Biological Sciences, University of Texas At El Paso, 79968, El Paso, TX, USA;Psychological and Brain Sciences, Program in Neuroscience, Indiana University, Bloomington, IN, USA;Psychological and Brain Sciences, Program in Neuroscience, Indiana University, Bloomington, IN, USA;Gill Center for Biomolecular Science, Indiana University, Bloomington, IN, USA;

关键词: Tonic immobility;    Behavioral arrest;    Reticular activating system;    Olfaction;    N;    PTSD;    Negative BOLD;   

DOI  :  10.1186/s12967-021-02891-6

来源: Springer

【 摘 要 】

BackgroundThe phytocannabinoid cannabidiol (CBD) exhibits anxiolytic activity and has been promoted as a potential treatment for post-traumatic stress disorders. How does CBD interact with the brain to alter behavior? We hypothesized that CBD would produce a dose-dependent reduction in brain activity and functional coupling in neural circuitry associated with fear and defense.MethodsDuring the scanning session awake mice were given vehicle or CBD (3, 10, or 30 mg/kg I.P.) and imaged for 10 min post treatment. Mice were also treated with the 10 mg/kg dose of CBD and imaged 1 h later for resting state BOLD functional connectivity (rsFC). Imaging data were registered to a 3D MRI mouse atlas providing site-specific information on 138 different brain areas. Blood samples were collected for CBD measurements.ResultsCBD produced a dose-dependent polarization of activation along the rostral-caudal axis of the brain. The olfactory bulb and prefrontal cortex showed an increase in positive BOLD whereas the brainstem and cerebellum showed a decrease in BOLD signal. This negative BOLD affected many areas connected to the ascending reticular activating system (ARAS). The ARAS was decoupled to much of the brain but was hyperconnected to the olfactory system and prefrontal cortex.ConclusionThe CBD-induced decrease in ARAS activity is consistent with an emerging literature suggesting that CBD reduces autonomic arousal under conditions of emotional and physical stress.

【 授权许可】

CC BY