AUTHOR=Lazarini-Lopes Willian , Do Val-da Silva Raquel A. , da Silva-Júnior Rui M. P. , Cunha Alexandra O. S. , Garcia-Cairasco Norberto 

TITLE=Cannabinoids in Audiogenic Seizures: From Neuronal Networks to Future Perspectives for Epilepsy Treatment

JOURNAL=Frontiers in Behavioral Neuroscience

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2021.611902

DOI=10.3389/fnbeh.2021.611902

ISSN=1662-5153

ABSTRACT=<p>Cannabinoids and <italic>Cannabis</italic>-derived compounds have been receiving especial attention in the epilepsy research scenario. Pharmacological modulation of endocannabinoid system's components, like cannabinoid type 1 receptors (CB1R) and their bindings, are associated with seizures in preclinical models. CB1R expression and functionality were altered in humans and preclinical models of seizures. Additionally, <italic>Cannabis</italic>-derived compounds, like cannabidiol (CBD), present anticonvulsant activity in humans and in a great variety of animal models. Audiogenic seizures (AS) are induced in genetically susceptible animals by high-intensity sound stimulation. Audiogenic strains, like the Genetically Epilepsy Prone Rats, Wistar Audiogenic Rats, and Krushinsky-Molodkina, are useful tools to study epilepsy. In audiogenic susceptible animals, acute acoustic stimulation induces brainstem-dependent wild running and tonic-clonic seizures. However, during the chronic protocol of AS, the audiogenic kindling (AuK), limbic and cortical structures are recruited, and the initially brainstem-dependent seizures give rise to limbic seizures. The present study reviewed the effects of pharmacological modulation of the endocannabinoid system in audiogenic seizure susceptibility and expression. The effects of <italic>Cannabis</italic>-derived compounds in audiogenic seizures were also reviewed, with especial attention to CBD. CB1R activation, as well <italic>Cannabis</italic>-derived compounds, induced anticonvulsant effects against audiogenic seizures, but the effects of cannabinoids modulation and <italic>Cannabis</italic>-derived compounds still need to be verified in chronic audiogenic seizures. The effects of cannabinoids and <italic>Cannabis</italic>-derived compounds should be further investigated not only in audiogenic seizures, but also in epilepsy related comorbidities present in audiogenic strains, like anxiety, and depression.</p>