RESUMEN
Dysfunction of GABAergic transmission related to abnormal expression of GABA(A) receptor subunits in specific brain regions underlies some pathological anxiety states. Besides involvement of the benzodiazepine recognition site of GABA(A) receptor in the expression of anxiety-like behaviour, the roles of the ß(2)/ß(3) subunits are not well characterized. To address this issue, the experimental design of this study utilized the GABAergic compound etifoxine (with a preferential effectiveness after binding to a specific site at ß(2)/ß(3) subunits) tested in two inbred mouse strains: BALB/cByJ and C57BL/6J mice using three behavioural paradigms (light/dark box, elevated plus maze and restraint stress-induced small intestinal transit inhibition) and the t-butylbicyclophosphorothionate-induced convulsions model. Etifoxine plasma and brain levels and ß(2)/ß(3) mRNAs and protein expression levels in various brain regions were compared between the two strains. The two mouse strains differed markedly in basal anxiety level. Etifoxine exhibited more pronounced anxiolytic and anticonvulsant effects in the BALB/cByJ mice compared to the C57BL/6J mice. The etifoxine brain/plasma ratios of the two strains were not different. Beta2 subunit mRNA and protein expression levels were around 25 and 10% higher respectively in the anterodorsal nucleus of the thalamus and the CA3 field of hippocampus of BALB/cByJ mice compared to C57BL/6J mice. Beta3 subunit mRNA and protein expression levels did not differ between the two strains. Based on these results, it is suggested that overexpression of GABA(A) receptor ß(2) subunit in BALB/cByJ mice relative to C57BL/6j mice contributes to the dysfunction in GABA(A) transmission in regions of brain known to regulate responses to stress. The dysregulated GABA(A) function in BALB/cByJ mice may be corrected by the administration of etifoxine.
Asunto(s)
Ansiolíticos/farmacología , Trastornos de Ansiedad/tratamiento farmacológico , Ansiedad/tratamiento farmacológico , Encéfalo/fisiopatología , Hipocampo/fisiopatología , Oxazinas/farmacología , Receptores de GABA-A/metabolismo , Convulsiones/tratamiento farmacológico , Animales , Ansiolíticos/sangre , Ansiolíticos/toxicidad , Conducta Animal/efectos de los fármacos , Encéfalo/fisiología , Hipocampo/fisiología , Intestino Delgado/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Oxazinas/sangre , Oxazinas/toxicidad , Receptores de GABA-A/genética , Convulsiones/fisiopatologíaRESUMEN
A simple and rapid enzyme linked immunosorbent assay (ELISA) to detect rabies antibodies in field fox sera has been standardised and established in several European laboratories. The same panels of 100 coded sera were investigated by four laboratories using this ELISA assay and reference serum neutralisation techniques (fluorescent antibody virus neutralisation (FAVN) test and rapid fluorescent focus inhibition test (RFFIT)). This indirect ELISA technique is highly correlated with conventional seroneutralisation test on cell culture. Results obtained with this ELISA test provide an almost perfect agreement between laboratories while the agreement of FAVN test and RFFIT results is substantial and very satisfactory. In view of this study, this simple and rapid ELISA test is a suitable tool for evaluating the sero-conversion rate in fox populations following oral rabies vaccination campaigns in European countries.