Tags

Type your tag names separated by a space and hit enter

CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations.
Epilepsy Res 2013; 106(1-2):74-82ER

Abstract

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.

Authors+Show Affiliations

Chair of Pharmacology, Department of Health Science, School of Medicine and Surgery, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23860329

Citation

Citraro, Rita, et al. "CB1 Agonists, Locally Applied to the Cortico-thalamic Circuit of Rats With Genetic Absence Epilepsy, Reduce Epileptic Manifestations." Epilepsy Research, vol. 106, no. 1-2, 2013, pp. 74-82.
Citraro R, Russo E, Ngomba RT, et al. CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations. Epilepsy Res. 2013;106(1-2):74-82.
Citraro, R., Russo, E., Ngomba, R. T., Nicoletti, F., Scicchitano, F., Whalley, B. J., ... 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. doi:10.1016/j.eplepsyres.2013.06.004.
Citraro R, et al. CB1 Agonists, Locally Applied to the Cortico-thalamic Circuit of Rats With Genetic Absence Epilepsy, Reduce Epileptic Manifestations. Epilepsy Res. 2013;106(1-2):74-82. PubMed PMID: 23860329.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations. AU - Citraro,Rita, AU - Russo,Emilio, AU - Ngomba,Richard T, AU - Nicoletti,Ferdinando, AU - Scicchitano,Francesca, AU - Whalley,Benjamin J, AU - Calignano,Antonio, AU - De Sarro,Giovambattista, Y1 - 2013/07/13/ PY - 2013/05/10/received PY - 2013/06/04/revised PY - 2013/06/18/accepted PY - 2013/7/18/entrez PY - 2013/7/19/pubmed PY - 2014/3/22/medline KW - Anandamide KW - CB receptors KW - Rimonabant KW - Seizure KW - WAG/Rij rats KW - WIN55,212 SP - 74 EP - 82 JF - Epilepsy research JO - Epilepsy Res. VL - 106 IS - 1-2 N2 - 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. SN - 1872-6844 UR - https://www.unboundmedicine.com/medline/citation/23860329/CB1_agonists_locally_applied_to_the_cortico_thalamic_circuit_of_rats_with_genetic_absence_epilepsy_reduce_epileptic_manifestations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0920-1211(13)00154-X DB - PRIME DP - Unbound Medicine ER -