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dc.contributor.authorLinge Méndez, Raquel
dc.contributor.authorJiménez Sánchez, Laura
dc.contributor.authorCampa, Leticia
dc.contributor.authorPilar Cuéllar, María Fuencisla 
dc.contributor.authorVidal Casado, Rebeca
dc.contributor.authorPazos Carro, Ángel 
dc.contributor.authorAdell Calduch, Albert
dc.contributor.authorDíaz Martínez, Álvaro 
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.description.abstractCannabidiol (CBD), the main non-psychotomimetic component of marihuana, exhibits anxiolytic-like properties in many behavioural tests, although its potential for treating major depression has been poorly explored. Moreover, the mechanism of action of CBD remains unclear. Herein, we have evaluated the effects of CBD following acute and chronic administration in the olfactory bulbectomy mouse model of depression (OBX), and investigated the underlying mechanism. For this purpose, we conducted behavioural (open field and sucrose preference tests) and neurochemical (microdialysis and autoradiography of 5-HT1A receptor functionality) studies following treatment with CBD. We also assayed the pharmacological antagonism of the effects of CBD to dissect out the mechanism of action. Our results demonstrate that CBD exerts fast and maintained antidepressant-like effects as evidenced by the reversal of the OBX-induced hyperactivity and anhedonia. In vivo microdialysis revealed that the administration of CBD significantly enhanced serotonin and glutamate levels in vmPFCx in a different manner depending on the emotional state and the duration of the treatment. The potentiating effect upon neurotransmitters levels occurring immediately after the first injection of CBD might underlie the fast antidepressant-like actions in OBX mice. Both antidepressant-like effect and enhanced cortical 5-HT/glutamate neurotransmission induced by CBD were prevented by 5-HT1A receptor blockade. Moreover, adaptive changes in pre- and post-synaptic 5-HT1A receptor functionality were also found after chronic CBD. In conclusion, our findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signalling through a 5-HT1A receptor-dependent mechanism.es_ES
dc.description.sponsorshipThis research was supported by Spanish Ministry of Economy and Competitiveness (SAF2011-25020), Instituto de Salud Carlos III (FIS Grant PI13-00038) co-funded by the European Regional Development Fund (‘A way to build Europe’) and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM).es_ES
dc.format.extent11 p.es_ES
dc.rights© 2016, Elsevier. Licensed under the Creative Commons Reconocimiento-NoComercial-SinObraDerivadaes_ES
dc.sourceNeuropharmacology. 2016 Apr;103:16-26es_ES
dc.subject.other5-HT(1A) receptores_ES
dc.subject.otherWAY-100635 maleate saltes_ES
dc.titleCannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptorses_ES
dc.title.alternative2. Cannabidiol enhancement of serotonergic and glutamatergic signalling in a mouse model of depression induces fast and maintained antidepressant actions: implication of 5-HT1A receptorses_ES

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© 2016, Elsevier. Licensed under the Creative Commons Reconocimiento-NoComercial-SinObraDerivadaExcept where otherwise noted, this item's license is described as © 2016, Elsevier. Licensed under the Creative Commons Reconocimiento-NoComercial-SinObraDerivada