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Title

Decreased GABAA and GABAB receptor functional activity in cannabinoid CB1 receptor knockout mice

AuthorsUrigüen, Leyre; García-Gutiérrez, María Salud; Manzanares, Jorge
Issue Date2011
PublisherSage Publications
CitationJournal of Psychopharmacology 25(1): 105-110 (2011)
AbstractThe interaction between brain GABAergic and endocannabinoid systems was evaluated by examining the quantitative and functional status of GABAergic receptors in cannabinoid CB1 receptor knockout (CB- 1 /- ) mice. To this aim, GABAA ([ 3H]-Muscimol binding assay), GABAB (baclofen-stimulated [35S]-GTPγS binding assay), GABAAα 1, GABAAα2 and GABAAγ 2 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 CB- 1 /- 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 transcriptase PCR was carried out for evaluating gene expression of α1, α2 and γ2 subunits of GABAA receptor in the amygdala. The results showed significant reduced GABAAα1 (50%) and GABA Aα2 (40%) receptor subunits gene expression in the amygdala of CB1 -/- mice. No difference was observed in GABAAγ2 receptor subunit gene expression. This study provides strong evidence of the involvement of CB1 receptors in the control of GABAergic responses mediated by GABAA and GABAB receptors, and suggests a possible role of the endocannabinoid system in the regulation of anxiety-related disorders. © 2011 The Author(s).
URIhttp://hdl.handle.net/10261/53205
DOI10.1177/0269881109358204
Identifiersdoi: 10.1177/0269881109358204
issn: 0269-8811
e-issn: 1461-7285
Appears in Collections:(IN) Artículos
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