Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K.
Pharmacol Rep
; 74(5): 1099-1106, 2022 Oct.
Article
em En
| MEDLINE
| ID: mdl-36112318
ABSTRACT
BACKGROUND:
The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been proposed to modulate seizures and might be recruited by CBD. Thus, we tested the hypothesis that the anticonvulsant effect of CBD involves PI3K in a seizure model induced by pentylenetetrazole (PTZ).METHODS:
We employed pharmacological and genetic approaches to inhibit PI3K and quantified its effects on seizure duration, latency, and number.RESULTS:
PI3K genetic ablation increased the duration and number of seizures. CBD inhibited PTZ-induced seizures in mice. Genetic deletion of PI3K or pretreatment with the selective inhibitor LY294002 prevented CBD effects.CONCLUSION:
Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pentilenotetrazol
/
Canabidiol
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Rep
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Brasil