Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/90325
Title: Synergistic action of CB1 and 5-HT2B receptors in preventing pilocarpine-induced status epilepticus in rats
Authors: Colangeli, Roberto
Di Maio, Roberto
Pierucci, Massimo
Deidda, Gabriele
Casarrubea, Maurizio
Di Giovanni, Giuseppe
Keywords: Status epilepticus
Receptors, Cannabinoid
Serotonin
Endocannabinoids
Pilocarpine
Issue Date: 2019-05
Publisher: Elsevier
Citation: Colangeli, R., Di Maio, R., Pierucci, M., Deidda, G., Casarrubea, M., & Di Giovanni, G. (2019). Synergistic action of CB1 and 5-HT2B receptors in preventing pilocarpine-induced status epilepticus in rats. Neurobiology of Disease, 125, 135-145.
Abstract: Endocannabinoids (eCBs) and serotonin (5-HT) play a neuromodulatory role in the central nervous system. Both eCBs and 5-HT regulate neuronal excitability and their pharmacological potentiation has been shown to control seizures in pre-clinical and human studies. Compelling evidence indicates that eCB and 5-HT systems interact to modulate several physiological and pathological brain functions, such as food intake, pain, drug addiction, depression, and anxiety. Nevertheless, there is no evidence of an eCB/5-HT interaction in experimental and human epilepsies, including status epilepticus (SE). Here, we performed video-EEG recording in behaving rats treated with the pro-convulsant agent pilocarpine (PILO), in order to study the effect of the activation of CB1/5-HT2 receptors and their interaction on SE. Synthetic cannabinoid agonist WIN55,212–2 (WIN) decreased behavioral seizure severity of PILO-induced SE at 2 mg/kg (but not at 1 and 5 mg/kg, i.p.), while 5-HT2B/2C receptor agonist RO60–0175 (RO; 1, 3, 10 mg/kg, i.p.) was devoid of any effect. RO 3 mg/kg was instead capable of potentiating the effect of WIN 2 mg/kg on the Racine scale score. Surprisingly, neither WIN 2 mg/kg nor RO 3 mg/kg had any effect on the incidence and the intensity of EEG seizures when administered alone. However, WIN+RO co-administration reduced the incidence and the severity of EEG SE and increased the latency to SE onset after PILO injection. WIN+RO effects were blocked by the selective CB1R antagonist AM251 and the 5-HT2BR antagonist RS127445, but not by the 5-HT2CR antagonist SB242084 or the 5-HT2AR antagonist MDL11,939. These data revealed a synergistic interaction between CB1R/5-HT2BR in the expression of PILO-induced SE.
URI: https://www.um.edu.mt/library/oar/handle/123456789/90325
Appears in Collections:Scholarly Works - FacM&SPB



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