Alvos moleculares e celulares do extrato padronizado de Ginkgo biloba L. na supressão condicionada ; Cellular and molecular targets of the standardized extract of Ginkgo biloba L. in conditioned suppression

The present study investigated the effect of the standardized extract of Ginkgo biloba (EGb) on the steps steps in the memory of fear and the extinction of fear memory. A proposal of foundations in multiple dose doses of extract; different times of treatment and acquisition of extract products; different times of treatment and pharmacological acquisitions by agonists and antagonists of serotonergic type 1A (5-HT1AR), glutamatergic receptors NMDA-type, 2B subunit (GluN2B-NMDA) and GABAA (GABAAR, α1 and α5 subunit) in animals submitted to the chest paradigm, assessed by conditioned suppression rate of licking response. Furthermore, we evaluated changes in gene expression (mRNA and protein) in the dorsal hippocampal formation, the amygdaloid complex, and the prefrontal cortex. Behavioral data suggest an EGb time and dose-dependent effect on modulation of 5-HT1A, GABAA and GluN2B-NMDA receptors as well as a glial fibial acidic protein (GFAP). The behavioural data from conditioned suppression ratio allow us to propose the effect of EGb as a nootropic agent because, in addition to not prevent the acquisition of fear memory, it modulates in a dose-dependent manner the extinction of conditioned fear. Our results show for the first time that the menmonic effect of EGb is correlated with differential expression of GluN2B-NMDA, GABAA-α1, GABAA-α5 receptors and GFAP in the dorsal hippocampal (DHF) and 5-HT1AR receptors in the layer CA3 of hippocampus. However, that either activation of GABAARs (Diazepam) or blocking of GluN2B-NMDAR (Ro 25-6981) or 5-HT1AR ((S) -WAY100135) resulted in impairment in memory acquisition and that treatment with high doses of EGb reversed the deficit by increasing the expression of GluN2B and/or GABAAR-α1 and α5 simultaneously in the CA1 region of the hippocampus. Our data added new insights into the role of α1 and α5 subunits of GABAA and GluN2B-NMDA receptors in DHF as an EGb target. In addition, they point to a parallel involvement of these receptors in the prelimbic (PrL) and infralimbic (IL) ...