Divergent Effects of Systemic and Intracollicular CB Receptor Activation Against Forebrain and Hindbrain-Evoked Seizures in Rats

Santos, Vítor; Hammack, Robert; Wicker, Evan; N’Gouemo, Prosper; Forcelli, Patrick A.

doi:10.3389/fnbeh.2020.595315

Cited by 7 publications

(3 citation statements)

References 65 publications

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“…However, a low expression of CB1R has been described in the IC of the GASH/Sal, the same thing that happens in other rodents (Moldrich and Wenger, 2000 ; Gerdeman and Lovinger, 2001 ). The activation of cannabinoid system in the IC through CB1 receptors can influence both GABAergic and glutamatergic neurons and exert a role in the modulation of motor behavior (Medeiros et al, 2016 ; Santos et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Distribution of the Cannabinoid Receptor Type 1 in the Brain of the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

Fuerte-Hortigón

Gonçalves

et al. 2021

Front. Behav. Neurosci.

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The endocannabinoid system modulates epileptic seizures by regulating neuronal excitability. It has become clear that agonist activation of central type I cannabinoid receptors (CB1R) reduces epileptogenesis in pre-clinical animal models of epilepsy. The audiogenic seizure-prone hamster GASH/Sal is a reliable experimental model of generalized tonic-clonic seizures in response to intense sound stimulation. However, no studies hitherto had investigated CB1R in the GASH/Sal. Although the distribution of CB1R has been extensively studied in mammalian brains, their distribution in the Syrian golden hamster brain also remains unknown. The objective of this research is to determine by immunohistochemistry the differential distribution of CB1R in the brains of GASH/Sal animals under seizure-free conditions, by comparing the results with wild-type Syrian hamsters as controls. CB1R in the GASH/Sal showed a wide distribution in many nuclei of the central nervous system. These patterns of CB1R-immunolabeling are practically identical between the GASH/Sal model and control animals, varying in the intensity of immunostaining in certain regions, being slightly weaker in the GASH/Sal than in the control, mainly in brain regions associated with epileptic networks. The RT-qPCR analysis confirms these results. In summary, our study provides an anatomical basis for further investigating CB1R in acute and kindling audiogenic seizure protocols in the GASH/Sal model as well as exploring CB1R activation via exogenously administered cannabinoid compounds.

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Section: Discussionmentioning

confidence: 99%

Distribution of the Cannabinoid Receptor Type 1 in the Brain of the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

Fuerte-Hortigón

Gonçalves

et al. 2021

Front. Behav. Neurosci.

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“…Similarly, central administration of CP 55940, a CB1/2 agonist, directly into the DLSC of GEPR-3s, suppressed seizures in 6/9 rats, reduced seizure severity in 2/9, and had no effect in 1/9. Additionally, intra-DLSC administration of SR141716 did not modify AS in control GEPRs and did not antagonize the anticonvulsant effects induced by systemic WIN 55,212-2 (Santos et al, 2020 ). Also using GEPRs, Samineni et al ( 2011 ) showed that central injection of AM251, a CB1R antagonist, directly into the ventrolateral PAG, attenuated post-ictal analgesia in GEPR-9s.…”

Section: Endocannabinoid System Modulation In Audiogenic Seizuresmentioning

confidence: 99%

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

Lazarini-Lopes

Silva

Silva-Júnior

et al. 2021

Front. Behav. Neurosci.

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Cannabinoids and Cannabis-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, Cannabis-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 Cannabis-derived compounds in audiogenic seizures were also reviewed, with especial attention to CBD. CB1R activation, as well Cannabis-derived compounds, induced anticonvulsant effects against audiogenic seizures, but the effects of cannabinoids modulation and Cannabis-derived compounds still need to be verified in chronic audiogenic seizures. The effects of cannabinoids and Cannabis-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.

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“…Similarly, CB1R antagonists induced Status Epilepticus-like activity in hippocampal neuronal culture [77]. Conversely, CB1R pharmacological activation suppressed acute audiogenic seizures in GEPR-3s [78] and protected juvenile rats from tonic-clonic seizures [79]. However, Hill et al [80] observed that Cannabis-derived compounds attenuated audiogenic brainstem seizures, independently of CB1R mechanisms, suggesting that much more complex mechanisms may be involved with CBD anticonvulsant effects.…”

Section: Discussionmentioning

confidence: 99%

Efeitos do tratamento com canabidiol (CBD) em modelos genéticos de epilepsias: estudos comportamentais, farmacológicos e eletrofisiológicos

Lopes¹

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Agradeço aos meus pais, Roberto e Cristina, pelo apoio, incentivo e suporte que sempre me deram. Agradeço à Gleice Kelli, minha companheira de vida, pela compreensão, apoio e convivência que tivemos durante todo esse tempo.Agradeço ao professor Dr. Norberto Garcia Cairasco pela oportunidade oferecida ao abrir as portas de seu laboratório, pela excelente mentoria, liberdade criativa e, acima de tudo, pela confiança em meu trabalho. Além de um orientador, tive um amigo ao longo desta trajetória.Agradeço aos meus colegas do Laboratório de Neurofisiologia e Neuroetologia Experimental (LNNE) pelos conhecimentos e ensinamentos compartilhados e pelos momentos alegres e descontraídos que sempre tivemos. Agradeço aos técnicos do LNNE, Flávio e José Antônio, por todo o suporte que me deram e por tudo que me ensinaram. Um agradecimento especial ao José Antônio pelos ensinamentos sobre modelos audiogênicos e análises neuroetológicas.Agradeço aos funcionários do Programa de Pós-Graduação em Neurologia e Neurociências da FMRP-USP, em especial à secretária Luci, pelo auxílio prestado durante meu Doutorado. Este agradecimento também se estende ao Departamento de Fisiologia da FMRP-USP.

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Divergent Effects of Systemic and Intracollicular CB Receptor Activation Against Forebrain and Hindbrain-Evoked Seizures in Rats

Cited by 7 publications

References 65 publications

Distribution of the Cannabinoid Receptor Type 1 in the Brain of the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

Distribution of the Cannabinoid Receptor Type 1 in the Brain of the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

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

Efeitos do tratamento com canabidiol (CBD) em modelos genéticos de epilepsias: estudos comportamentais, farmacológicos e eletrofisiológicos

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