RGD Reference Report - Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat. - Rat Genome Database

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Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat.

Authors: Rizzo, V  Ferraro, G  Carletti, F  Lonobile, G  Cannizzaro, C  Sardo, P 
Citation: Rizzo V, etal., Neurosci Lett. 2009 Sep 22;462(2):135-9. Epub 2009 Jul 10.
RGD ID: 2314658
Pubmed: PMID:19595742   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neulet.2009.07.014   (Journal Full-text)

The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB(1) 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-pyr azole-3-carboxamide (AM251, selective CB(1) antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation - MDA) in the rat. WIN55,212-2 (21mgkg(-1)) exerted an anticonvulsant effect, significantly reduced by the pre-treatment with AM251 (1mgkg(-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 CB(1) 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 CB(1) receptor activation or to the involvement of further receptor subtypes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
focal epilepsy  ISOCnr1 (Rattus norvegicus)2314658; 2314658 RGD 
focal epilepsy  IMP 2314658 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cnr1  (cannabinoid receptor 1)

Genes (Mus musculus)
Cnr1  (cannabinoid receptor 1)

Genes (Homo sapiens)
CNR1  (cannabinoid receptor 1)


Additional Information