Detalle de: Decreased GABA A and GABA B receptor functional activity in cannabinoid CB 1 receptor knockout mice

The interaction between brain GABAergic and endocannabinoid systems was evaluated by examining the quantitative and functional status of GABAergic receptors in cannabinoid CB 1 receptor knockout (CB 1 -/- ) mice. To this aim, GABA A ([ 3 H]-Muscimol binding assay), GABA B (baclofen-stimulated [ 35 S]-GTPγS binding assay), GABA A α 1 , GABA A α 2 and GABA A γ 2 receptors gene expression (real-time reverse transcriptase polymerase chain reaction [PCR]) were carried out in CB 1 -/- and wild-type mice (CB 1 +/+ ). [ 3 H]-Muscimol binding assays revealed significant reduction in the density of GABA A receptors in CA2 (30%) and DG (28%) of the hippocampus, thalamus (40%), cingulate (28%) and motor cortex (35%) of CB 1 -/- mice. Functional activity of metabotropic GABA B receptors was measured by evaluating the ability of GABA B agonist baclofen to stimulate [ 35 S]-GTPγS binding. The results showed significant reduced [ 35 S]-GTPγS binding in CA1 (61%), CA3 (51%) and DG (60%) of CB 1 -/- mice compared with CB 1 +/+ mice. Real-time reverse transcriptase PCR was carried out for evaluating gene expression of α 1 , α 2 and γ 2 subunits of GABA A receptor in the amygdala. The results showed significant reduced GABA A α 1 (50%) and GABA A α 2 (40%) receptor subunits gene expression in the amygdala of CB 1 -/- mice. No difference was observed in GABA A γ 2 receptor subunit gene expression. This study provides strong evidence of the involvement of CB 1 receptors in the control of GABAergic responses mediated by GABA A and GABA B receptors, and suggests a possible role of the endocannabinoid system in the regulation of anxiety-related disorders.