CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations

Citraro, R., Russo, E., Ngomba, R.T. , Nicoletti, F., Scicchitano, F., Whalley, B.J., Calignano, A. and De Sarro, G. (2013) CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations. Epilepsy Research, 106 (1-2). pp. 74-82. ISSN 0920-1211

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Drugs that modulate the endocannabinoid system and endocannabinoids typically play an anticonvulsant role although some proconvulsant effects have been reported both in humans and animal models. Moreover, no evidence for a role of the cannabinoid system in human absence epilepsy has been found although limited evidence of efficacy in relevant experimental animal models has been documented. This study aims to characterize the role of cannabinoids in specific areas of the cortico-thalamic network involved in oscillations that underlie seizures in a genetic animal model of absence epilepsy, the WAG/Rij rat. We assessed the effects of focal injection of the endogenous cannabinoid, anandamide (AEA), a non-selective CB receptor agonist (WIN55,212) and a selective CB1 receptor antagonist/inverse agonist (SR141716A) into thalamic nuclei and primary somatosensory cortex (S1po) of the cortico-thalamic network.AEA and WIN both reduced absence seizures independently from the brain focal site of infusion while, conversely, rimonabant increased absence seizures but only when focally administered to the ventroposteromedial thalamic nucleus (VPM). These results, together with previous reports, support therapeutic potential for endocannabinoid system modulators in absence epilepsy and highlight that attenuated endocannabinergic function may contribute to the generation and maintenance of seizures. Furthermore, the entire cortico-thalamic network responds to cannabinoid treatment, indicating that in all areas considered, CB receptor activation inhibits the pathological synchronization that subserves absence seizures. In conclusion, our result might be useful for the identification of future drug therapies in absence epilepsy.

Keywords:2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo1,2,3 de1,4benzoxazine, anandamide, cannabinoid 1 receptor agonist, rimonabant, absence, animal experiment, animal model, article, controlled study, drug effect, genetic absence epilepsy, genetic disorder, genetic model, male, nonhuman, oscillation, priority journal, rat, somatosensory cortex, thalamus nucleus, ventroposteromedial thalamic nucleus, Anandamide, CB receptors, Rimonabant, Seizure, WAG/Rij rats, WIN55,212, Animals, Anticonvulsants, Arachidonic Acids, Benzoxazines, Cannabinoid Receptor Agonists, Cerebral Cortex, Electroencephalography, Endocannabinoids, Epilepsy, Epilepsy, Absence, Injections, Intraventricular, Morpholines, Naphthalenes, Neural Pathways, Piperidines, Polyunsaturated Alkamides, Pyrazoles, Rats, Receptor, Cannabinoid, CB1, Seizures, Thalamus
Subjects:B Subjects allied to Medicine > B210 Pharmacology
B Subjects allied to Medicine > B140 Neuroscience
Divisions:College of Science > School of Pharmacy
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ID Code:22146
Deposited On:04 Feb 2016 15:43

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