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Cannabinoid receptor 1/2 double‐knockout mice develop epilepsy
Author(s) -
Rowley Shane,
Sun Xiaofei,
Lima Isabel V.,
Tavenier Alexandra,
Oliveira Antonio Carlos Pinheiro,
Dey Sudhansu K.,
Danzer Steve C.
Publication year - 2017
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13930
Subject(s) - cannabinoid receptor , endocannabinoid system , cannabinoid , knockout mouse , cannabinoid receptor type 2 , neuroscience , epilepsy , receptor , pharmacology , biology , medicine , agonist
Summary The endocannabinoid system has gained attention as an important modulator of activity in the central nervous system. Initial studies focused on cannabinoid receptor 1 ( CB 1), which is widely expressed in the brain, but recent work also implicates cannabinoid receptor 2 ( CB 2) in modulating neuronal activity. Both receptors are capable of reducing neuronal activity, generating interest in cannabinoid receptor agonists as potential anticonvulsants. CB 1 ( Cnr1 ) and CB 2 ( Cnr2 ) single‐knockout mice have been generated, with the former showing heightened seizure sensitivity, but not overt seizures. Given overlapping and complementary functions of CB 1 and CB 2 receptors, we queried whether double‐knockout mice would show an exacerbated neurological phenotype. Strikingly, 30% of double‐knockout mice exhibited provoked behavioral seizures, and 80% were found to be epileptic following 24/7 video‐electroencephalographic monitoring. Single‐knockout animals did not exhibit seizures. These findings highlight the importance of the endocannabinoid system for maintaining network stability.