Cannabidiol improves survival and behavioural co‐morbidities of Dravet syndrome in mice

Autor: Michael Bazelot, Eleni Serafeimidou-Pouliou, Pabitra Hriday Patra, Alister J. McNeish, Claire M. Williams, Benjamin J. Whalley
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: British Journal of Pharmacology
Patra, P H, Serafeimidou-Pouliou, E, Bazelot, M, Whalley, B J, Williams, C M & McNeish, A J 2020, ' Cannabidiol improves survival and behavioural co-morbidities of Dravet syndrome in mice ', British Journal of Pharmacology, vol. 177, no. 12, pp. 2779-2792 . https://doi.org/10.1111/bph.15003
ISSN: 1476-5381
0007-1188
DOI: 10.1111/bph.15003
Popis: Background and Purpose Dravet syndrome is a severe, genetic form of paediatric epilepsy associated with premature mortality and comorbidities such as anxiety, depression, autism, motor dysfunction, and memory deficits. Cannabidiol is an approved anticonvulsive drug in USA and Europe for seizures associated with Dravet syndrome therapy in patients 2 years of age and older; we investigated its potential to prevent premature mortality and improve associated comorbidities. Experimental Approach The efficacy of sub-chronic cannabidiol administration in two mouse models which reproduce characteristics of Dravet syndrome was investigated. The effect of cannabidiol on neonatal welfare and survival was studied using Scn1a-/- mice. We then used a hybrid, heterozygote Scn1a+/- mouse model to study the effect of cannabidiol on survival and behavioural comorbidities; motor deficits (rotarod and static-beam test), gait abnormality (gait test), social anxiety (social interaction test), anxiety-like (elevated plus maze) and depressive-like behaviours (sucrose preference test) and cognitive impairment (radial arm maze test). Key Results In Scn1a-/- mice, cannabidiol increased survival and delayed worsening of neonatal welfare. In Scn1a+/- mice chronic cannabidiol administration did not show any adverse effect on motor function and gait, reduced premature mortality, improved social behaviour and memory function, and reduced anxiety-like and depressive-like behaviours. Conclusion and Implications We are the first to demonstrate a potential disease-modifying effect of cannabidiol in animal models of Dravet syndrome. cannabidiol treatment reduced premature mortality and improved several behavioural comorbidities in Dravet syndrome mice. These crucial findings may be translated into human therapy to address behavioural comorbidities associated with Dravet syndrome.
Databáze: OpenAIRE
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