O papel dos canabinóides no controle das crises epilépticas em animais neonatos

Abstract

Epilepsy is a chronic neurological disorder that manifests itself through epileptic seizures, classified as focal or generalized. Although medications such as Phenobarbital (PB) exist to control seizures, they have been shown to be insufficient to fully suppress all epileptic seizures and can lead to neuronal death in immature brains. Cannabidiol (CBD) and Cannabigerol (CBG), both components extracted from Cannabis sativa, may be possible solutions due to their anti-seizure and neuroprotective potential. Both modulate the activity of the Endocannabinoid System, being important in the control of neuronal excitation and neuroinflammation. Therefore, we sought to demonstrate the anti-seizure effects of CBD and CBG treatments in a Pentylenetetrazole (PTZ) model in rodents with developing brains. Wistar rats were used at the ages of 10 days (P10) and 21 days (P21) after birth. The doses of CBD (3 mg/kg, 30 mg/kg, 100 mg/kg and 200 mg/kg (ip)) were evaluated, as well as their interaction with BP, at doses 3 mg/kg, 10 mg/kg, 30 mg/kg and 75 mg/kg (ip), in neonatal rats (P10). Also, CBG doses (2 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, 100 mg/kg and 200 mg/kg (ip)) were tested in P10 and P21 rats. In addition, the mechanism of anticonvulsant action exerted by CBG in P10 rats was evaluated. The results show that CBD (30 mg/kg) may have significantly potentiated the anticonvulsant capacity of PB (10 mg/kg). Also, the 100 mg/kg and 200 mg/kg doses of CBD may have significantly potentiated the anticonvulsant capacity of PB, when applied at doses 3 mg/kg and 10 mg/kg. In addition, in general, P10 animals that received 30 mg/kg and 100 mg/kg of CBG had a significantly shorter seizure duration, showing the potential anticonvulsant effect of such a drug. Also, P21 animals that received 200 mg/kg of CBG had a higher latency to the onset of seizures, thus evidencing the efficacy of the drug. Regarding the anticonvulsant mechanism of action effected by CBG, rats given the 3 mg/kg (ip) dose of Cannabinoid Type I (CB1) and Transient Vanilloid Potential I (TRPV1) receptor antagonists, combined with the 100 mg/kg (ip) dose of CBG, generally had a significantly shorter duration of the most severe PTZ-induced seizures, it may mean that CBG is acting on other receptors that justify its anticonvulsant effect in P10 animals. The results show that depending on the dose, CBD combined with PB, and CBG, are efficient in controlling induced seizures in P10 and P21 rats.