CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors

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• dc.contributor.author Mato, Susanaca
• dc.contributor.author Aso Pérez, Ester
• dc.contributor.author Castro, Elena
• dc.contributor.author Martín, Miguel
• dc.contributor.author Valverde Granados, Olga
• dc.contributor.author Maldonado, Rafael, 1961-
• dc.contributor.author Pazos, Ángel
• dc.date.accessioned 2011-07-27T08:27:45Z
• dc.date.available 2011-07-27T08:27:45Z
• dc.date.issued 2007ca
• dc.description.abstract Interaction between brain endocannabinoid (EC) and serotonin (5-HT) systems was investigated by examining 5-HT-dependent behavioural and biochemical responses in CB1 receptor knockout mice. CB1 knockout animals exhibited a significant reduction in the induction of head twitches and paw tremor by the 5-HT2A receptor selective agonist ()DOI, as well as a reduced hypothermic response following administration of the 5-HT1A receptor agonist (±)-8-OH-DPAT. Additionally, exposure to the tail suspension test induced enhanced despair responses in CB1 knockout mice. However, the tricyclic antidepressant imipramine and the 5-HT selective reuptake inhibitor fluoxetine induced similar decreases in the time of immobility in the tail suspension test in CB1 receptor knockout and wild-type mice. No differences were found between both genotypes with regard to 5-HT2A receptor and 5-HT1A receptors levels, measured by autoradiography in different brain areas. However, a significant decrease in the ability of the 5-HT1A receptor agonist (±)-8-OH-DPAT to stimulate 35SGTPS binding was detected in the hippocampal CA1 area of CB1 receptor knockout mice. This study provides evidence that CB1 receptors are involved in the regulation of serotonergic responses mediated by 5-HT2A and 5-HT1A receptors, and suggests that a reduced coupling of 5-HT1A receptors to Gi/o proteins in the hippocampus might be involved in these effects.
• dc.description.sponsorship S. Mato and E. Aso were recipients of predoctoral fellowships from the Marqués de Valdecilla Foundation and the Spanish MCYT (BES-2005-8265), respectively. E. Castro is a fellow researcher under an University of Cantabria- Faes Farma contract. The technical assistance of Ms. Lourdes Lanza and Ms. Josefa Castillo is kindly acknowledged. This study was partially supported by Ministerio de Ciencia y Tecnología (CICYT SAF04-00941 to AP; SAF2004/0568 to OV; BFU2004/00920BFI to RM,and GEN2003-20651-C06-06 to RM), the European Communities (NEWMOOD LSHM-CT-2003 5003474 to RM) and Generalitat de Catalunya (2005SGR00131 to RM)
• dc.format.mimetype application/pdfca
• dc.identifier.citation Mato S, Aso E, Castro E, Martín M, Valverde O, Maldonado R et al. CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors. J Neurochem. 2007;103:2111–20. DOI: 10.1111/j.1471-4159.2007.04961.x
• dc.identifier.doi http://dx.doi.org/10.1111/j.1471-4159.2007.04961.x
• dc.identifier.issn 0022-3042
• dc.identifier.uri http://hdl.handle.net/10230/12418
• dc.language.iso engca
• dc.publisher Wiley-Blackwellca
• dc.relation.ispartof Journal of Neurochemistry. 2007;103(5):2111-20
• dc.rights © 2007 Ester Asp et al. Journal Compilation © 2007 International Society for Neurochemistry
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword CB1 receptors
• dc.subject.keyword 5-HT1A receptors
• dc.subject.keyword 5-HT2A receptors
• dc.subject.keyword Antidepressants
• dc.subject.other Serotonina
• dc.subject.other Cannabinoides -- Receptors
• dc.subject.other Cannabinoides -- Efectes fisiològics
• dc.title CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptorsca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/submittedVersion