Journal
NEUROSCIENCE LETTERS
Volume 462, Issue 2, Pages 135-139Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2009.07.014
Keywords
Rat; Maximal dentate activation; Epilepsy; Control; Cannabinoids
Categories
Funding
- Italian Ministry of the University
- Scientific and Technologic Research, Rome, Italy
Ask authors/readers for more resources
The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB1 receptor. This study evaluates the anticonvulsant activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB1 antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation - MDA) in the rat. WIN55,212-2 (21 mg kg(-1)) exerted an anticonvulsant effect, significantly reduced by the pretreatment with AM251 (1 mg kg(-1), 30 min interval). Surprisingly, AM251, administered alone at the same dose, failed to induce any modification in MDA responses. Our data suggest the involvement of the CB system in the inhibitory control of hyperexcitability phenomena in a model of acute partial epilepsy. Although the MDA model per se does not induce a basal activation of CB1 receptors, as suggested by the lack of efficacy of AM251 when administered alone, the partial suppression of WIN55,212-2-induced effects in rats pre-treated with AM251 allows to hypothesise that the WIN55,212-2-induced antiepileptic effect is strictly linked to an increased CB1 receptor activation or to the involvement of further receptor subtypes. (c) 2009 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available