Chronic cannabidiol (CBD) administration induces anticonvulsant and antiepileptogenic effects in a genetic model of epilepsy

Lazarini-Lopes, Willian; Silva, Raquel A. Do Val-da; Silva-Júnior, Rui Milton Patrício da; Silva-Cardoso, Gleice Kelli; Leite–Panissi, Christie Ramos Andrade; Leite, João P.; García-Cairasco, Norberto

doi:10.1016/j.yebeh.2021.107962

Cited by 12 publications

(7 citation statements)

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“…Nevertheless, the hippocampus of WARs does present neuroplastic alterations associated with epilepsy susceptibility and neuropsychiatric alterations, such as reduced GABAergic currents in hippocampal neurons [ 80 , 81 ], increased CB1 expression [ 53 ], hippocampal hyperplasia [ 82 ], and increased calcium concentration in hippocampal synaptosomes [ 83 ]. The amygdaloid complex, especially the BLA, is probably the limbic structure most susceptible to AK epileptogenic events, presenting neuronal loss and increased neo-Timm+ staining (Zn + sprouting) [ 58 ], as well as increased neuronal hyperactivity and CB1 expression [ 53 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…The slides were mounted in Vectashield mounting medium (Vector Laboratories, Burlingame, CA, USA) and stored at 4 °C. Immunostaining for FosB+ neurons were performed in the ICx, DLSC, dPAG, and BLA as previously described [ 57 ]. Briefly, free-floating sections were washed in PBS and incubated overnight in a rabbit polyclonal primary antibody (1:1000; sc-48, Santa Cruz Biotechnology, Dallas, TX, USA) diluted in a 2% solution of bovine serum albumin solution (BSA, Amresco, Solon, OH, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Immunoreactive sites were visualized and photographed in a scanning microscope (Olympus BX61VS). Tissues processed for TRPV1R immunofluorescence and FosB+ neurons were analyzed in 400× magnification and the software ImageJ (National Institute of Mental Health, Bethesda, MD, USA) was used for image processing analysis as we previously described [ 56 , 57 ].…”

Section: Methodsmentioning

confidence: 99%

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Increased TRPV1 Channels and FosB Protein Expression Are Associated with Chronic Epileptic Seizures and Anxiogenic-like Behaviors in a Preclinical Model of Temporal Lobe Epilepsy

et al. 2022

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Epilepsies are neurological disorders characterized by chronic seizures and their related neuropsychiatric comorbidities, such as anxiety. The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel has been implicated in the modulation of seizures and anxiety-like behaviors in preclinical models. Here, we investigated the impact of chronic epileptic seizures in anxiety-like behavior and TRPV1 channels expression in a genetic model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. WARs were submitted to audiogenic kindling (AK), a preclinical model of temporal lobe epilepsy (TLE) and behavioral tests were performed in the open-field (OF), and light-dark box (LDB) tests 24 h after AK. WARs displayed increased anxiety-like behavior and TRPV1R expression in the hippocampal CA1 area and basolateral amygdala nucleus (BLA) when compared to control Wistar rats. Chronic seizures increased anxiety-like behaviors and TRPV1 and FosB expression in limbic and brainstem structures involved with epilepsy and anxiety comorbidity, such as the hippocampus, superior colliculus, and periaqueductal gray matter. Therefore, these results highlight previously unrecognized alterations in TRPV1 expression in brain structures involved with TLE and anxiogenic-like behaviors in a genetic model of epilepsy, the WAR strain, supporting an important role of TRPV1 in the modulation of neurological disorders and associated neuropsychiatric comorbidities.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Increased TRPV1 Channels and FosB Protein Expression Are Associated with Chronic Epileptic Seizures and Anxiogenic-like Behaviors in a Preclinical Model of Temporal Lobe Epilepsy

et al. 2022

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“…It is important to highlight that the chronic administration of CBD alone might markedly induce anticonvulsant and antiepileptogenic effects [40]. However, the crucial role of the volatile component of K2 in the overall activity of the extract, together with the presence of CBD, could be supported by the fact that CBD alone, at a low dose, seemed not to be effective [41].…”

Section: Discussionmentioning

confidence: 99%

Antiseizure Effects of Fully Characterized Non-Psychoactive Cannabis sativa L. Extracts in the Repeated 6-Hz Corneal Stimulation Test

et al. 2021

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Compounds present in Cannabis sativa L. preparations have recently attracted much attention in the treatment of drug-resistant epilepsy. Here, we screened two olive oil extracts from a non-psychoactive C. sativa variety, fully characterized by high-performance liquid chromatography and gas chromatography. Particularly, hemp oils with different concentrations of terpenes were administered at the same dose of cannabidiol (25 mg/kg/day orally), 1 h before the 6-Hz corneal stimulation test (44 mA). Mice were stimulated once a day for 5 days and evaluated by video-electrocorticographic recordings and behavioral analysis. Neuronal activation was assessed by FosB/ΔFosB immunoreactivity. Both oils significantly reduced the percentage of mice experiencing convulsive seizures in comparison to olive oil-treated mice (p < 0.050; Fisher’s exact test), but only the oil enriched with terpenes (K2) significantly accelerated full recovery from the seizure. These effects occurred in the presence of reduced power of delta rhythm, and, instead, increased power of theta rhythm, along with a lower FosB/ΔFosB expression in the subiculum (p < 0.050; Duncan’s method). The overall findings suggest that both cannabinoids and terpenes in oil extracts should be considered as potential therapeutic agents against epileptic seizures and epilepsy.

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“…These studies suggest a protective effect of CBD against seizure-induced cell death. In Wister audiogenic rats, chronic CBD treatment (25 mg/kg, i.p., twice a day for 10 days) significantly suppressed the development of seizure responses in audiogenic kindling, indicating the antiepileptogenic effect of CBD in audiogenic kindling model ( Lazarini-Lopes et al, 2021 ). Moreover, CBD treatment (200 mg/kg, orally administered) after the onset of spontaneous recurrent seizures in a pilocarpine-induced SE model not only suppressed seizure frequency but also ameliorated reference memory and working memory errors of epileptic mice in the hole-board task ( Patra et al, 2019 ).…”

Section: Cannabidiolmentioning

confidence: 93%

Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures

Sugaya

Kano

2022

Front. Neural Circuits

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Research on endocannabinoid signaling has greatly advanced our understanding of how the excitability of neural circuits is controlled in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses excitability by inhibiting glutamate release, while that at inhibitory synapses promotes excitability by inhibiting GABA release, although there are some exceptions in genetically epileptic animal models. In the epileptic brain, the physiological distributions of endocannabinoid signaling molecules are disrupted during epileptogenesis, contributing to the occurrence of spontaneous seizures. However, it is still unknown how endocannabinoid signaling changes during seizures and how the redistribution of endocannabinoid signaling molecules proceeds during epileptogenesis. Recent development of cannabinoid sensors has enabled us to investigate endocannabinoid signaling in much greater spatial and temporal details than before. Application of cannabinoid sensors to epilepsy research has elucidated activity-dependent changes in endocannabinoid signaling during seizures. Furthermore, recent endocannabinoid research has paved the way for the clinical use of cannabidiol for the treatment of refractory epilepsy, such as Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Cannabidiol significantly reduces seizures and is considered to have comparable tolerability to conventional antiepileptic drugs. In this article, we introduce recent advances in research on the roles of endocannabinoid signaling in epileptic seizures and discuss future directions.

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Chronic cannabidiol (CBD) administration induces anticonvulsant and antiepileptogenic effects in a genetic model of epilepsy

Cited by 12 publications

References 77 publications

Increased TRPV1 Channels and FosB Protein Expression Are Associated with Chronic Epileptic Seizures and Anxiogenic-like Behaviors in a Preclinical Model of Temporal Lobe Epilepsy

Increased TRPV1 Channels and FosB Protein Expression Are Associated with Chronic Epileptic Seizures and Anxiogenic-like Behaviors in a Preclinical Model of Temporal Lobe Epilepsy

Antiseizure Effects of Fully Characterized Non-Psychoactive Cannabis sativa L. Extracts in the Repeated 6-Hz Corneal Stimulation Test

Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures

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