Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: The efficacy of sub-chronic cannabidiol administration in two mouse models 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 co-morbidities: 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 co-morbidities in Dravet syndrome mice. These crucial findings may be translated into human therapy to address behavioural co-morbidities associated with Dravet syndrome.
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Authors | Pabitra Hriday Patra, Eleni Serafeimidou-Pouliou, Michael Bazelot, Benjamin Jason Whalley, Claire Michelle Williams, Alister James McNeish |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 177
Issue 12
Pg. 2779-2792
(06 2020)
ISSN: 1476-5381 [Electronic] England |
PMID | 32321192
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. |
Chemical References |
- NAV1.1 Voltage-Gated Sodium Channel
- Scn1a protein, mouse
- Cannabidiol
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Topics |
- Animals
- Cannabidiol
(pharmacology, therapeutic use)
- Child
- Epilepsies, Myoclonic
(drug therapy, genetics)
- Humans
- Mice
- Morbidity
- NAV1.1 Voltage-Gated Sodium Channel
(genetics)
- Seizures
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