Decreased GABAA and GABAB receptor functional activity in cannabinoid CB1 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 CB1 receptor knockout (CB1-/-) mice. To this aim, GABAA ([3H]-Muscimol binding assay), GABAB (baclofen-stimulated [35S]-GTPγS binding assay), GABAAα1, GABAAα2 and GABAAγ2 receptors gene expression (real-time reverse transcriptase polymerase chain reaction [PCR]) were carried out in CB1-/- and wild-type mice (CB1+/+). [3H]-Muscimol binding assays revealed significant reduction in the density of GABAA receptors in CA2 (30%) and DG (28%) of the hippocampus, thalamus (40%), cingulate (28%) and motor cortex (35%) of CB1-/- mice. Functional activity of metabotropic GABAB receptors was measured by evaluating the ability of GABAB agonist baclofen to stimulate [35S]-GTPγS binding. The results showed significant reduced [35S]-GTPγS binding in CA1 (61%), CA3 (51%) and DG (60%) of CB1-/- mice compared with CB1+/+ mice. Real-time reverse transcripta...