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Título: | Overexpression of CB2 cannabinoid receptors decreased vulnerability to anxiety and impaired anxiolytic action of alprazolam in mice |
Autor: | García-Gutiérrez, María Salud CSIC ORCID; Manzanares, Jorge CSIC ORCID CVN | Palabras clave: | Benzodiazepines Cannabinoid CB2r CRF gene expression GABAAα2 GABAAγ2 POMC gene expression Transgenic mice |
Fecha de publicación: | ene-2011 | Editor: | Sage Publications | Citación: | Journal of Psychopharmacology 25(1): 111-120 (2011) | Resumen: | Mice overexpressing CB2r (CB2xP) were exposed to open field (OF), light-dark box (LDB) and elevated plus maze (EPM) tests. Corticotropin-releasing factor (CRF) and pro-opiomelanocortin (POMC) mRNA were measured in paraventricular (PVN) and arcuate (ARC) nuclei of the hypothalamus after 30 minutes of restraint stress (RS). Anxiolytic effects of alprazolam (45 or 70 μg/kg, ip) were evaluated. GABA A α 2 and GABA Aγ 2 mRNA were measured in the hippocampus (HIPP) and amygdala (AMY) of CB2xP and wild type (WT) mice. No differences were observed in the total distance travelled by CB2xP and WT mice in OF. Central and peripheral distances travelled significantly increased and decreased in CB2xP mice. Overexpression of CB2r reduced anxiety-like behaviours in LDB and EPM. In WT mice, RS increased CRF (82%) and POMC (42%) mRNA in the PVN and ARC nuclei, respectively. In CB2xP mice, RS also increased POMC (22%) mRNA in the ARC nucleus, but had no effect on CRF mRNA in the PVN nucleus. Administration of alprazolam was without effect in CB2xP mice. An increase of GABA Aα 2 and GABA Aγ 2 mRNA in the hippocampus and amygdala of CB2xP mice was observed. Our findings revealed that increased expression of CB2r significantly reduced anxiogenic-related behaviours, modified the response to stress and impaired the action of anxiolytic drugs. | Versión del editor: | http://dx.doi.org/10.1177/0269881110379507 | URI: | http://hdl.handle.net/10261/55010 | DOI: | 10.1177/0269881110379507 | ISSN: | 0269-8811 | E-ISSN: | 1461-7285 |
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