Role of CB2 cannabinoid receptors in the rewarding, reinforcing, and physical effects of nicotine

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• dc.contributor.author Navarrete, Franciscoca
• dc.contributor.author Rodríguez Arias, Martaca
• dc.contributor.author Martín García, Elena, 1975-ca
• dc.contributor.author Navarro, Danielaca
• dc.contributor.author García Gutiérrez, Susanaca
• dc.contributor.author Aguilar Morón, María Asunciónca
• dc.contributor.author Aracil Fernández, Auxiliadoraca
• dc.contributor.author Berbel, Pereca
• dc.contributor.author Miñarro, Joséca
• dc.contributor.author Maldonado, Rafael, 1961-ca
• dc.contributor.author Manzanares, Jorgeca
• dc.date.accessioned 2015-04-01T07:31:38Z
• dc.date.available 2015-04-01T07:31:38Z
• dc.date.issued 2013ca
• dc.description.abstract This study was aimed to evaluate the involvement of CB2 cannabinoid receptors (CB2r) in the rewarding, reinforcing and motivational effects of nicotine. Conditioned place preference (CPP) and intravenous self-administration experiments were carried out in knockout mice lacking CB2r (CB2KO) and wild-type (WT) littermates treated with the CB2r antagonist AM630 (1 and 3 mg/kg). Gene expression analyses of tyrosine hydroxylase (TH) and α3- and α4-nicotinic acetylcholine receptor subunits (nAChRs) in the ventral tegmental area (VTA) and immunohistochemical studies to elucidate whether CB2r colocalized with α3- and α4-nAChRs in the nucleus accumbens and VTA were performed. Mecamylamine-precipitated withdrawal syndrome after chronic nicotine exposure was evaluated in CB2KO mice and WT mice treated with AM630 (1 and 3 mg/kg). CB2KO mice did not show nicotine-induced place conditioning and self-administered significantly less nicotine. In addition, AM630 was able to block (3 mg/kg) nicotine-induced CPP and reduce (1 and 3 mg/kg) nicotine self-administration. Under baseline conditions, TH, α3-nAChR, and α4-nAChR mRNA levels in the VTA of CB2KO mice were significantly lower compared with WT mice. Confocal microscopy images revealed that CB2r colocalized with α3- and α4-nAChRs. Somatic signs of nicotine withdrawal (rearings, groomings, scratches, teeth chattering, and body tremors) increased significantly in WT but were absent in CB2KO mice. Interestingly, the administration of AM630 blocked the nicotine withdrawal syndrome and failed to alter basal behavior in saline-treated WT mice. These results suggest that CB2r play a relevant role in the rewarding, reinforcing, and motivational effects of nicotine. Pharmacological manipulation of this receptor deserves further consideration as a potential new valuable target for the treatment of nicotine dependence.
• dc.description.sponsorship This study was supported by the following research grants: Ministerio de Ciencia e Innovación (SAF2011-23420 to Jorge Manzanares, SAF2009-10689 to Pere Berbel, and SAF2011-29864 to Rafael Maldonado); Ministerio de Economía y Competitividad, Dirección General de Investigación (PSI2011-24762) to José Miñarro; Generalidad Valenciana, Consejería de Educación (PROMETEO/2009/072) to José Miñarro; Gobierno Catalán (SGR2009-00131) to Rafael Maldonado; ICREA Academia-2008 to Rafael Maldonado; and Instituto de Salud ‘Carlos III’ (FIS), RETICS, Red de Trastornos Adictivos (RD06/0001/1004, RD12/0028/0019 to Jorge Manzanares; RD06/001/0016, RD12/0028/005 to José Miarro; RD06/001/001, RD12/0028/0023 to Rafael Maldonado)
• dc.format.mimetype application/pdfca
• dc.identifier.citation Navarrete F, Rodríguez-Arias M, Martín-García E, Navarro D, García-Gutiérrez MS, Aguilar MA et al. Role of CB2 cannabinoid receptors in the rewarding, reinforcing, and physical effects of nicotine. Neuropsychopharmacology. 2013 Nov;38(12):2515-24. DOI: 10.1038/npp.2013.157ca
• dc.identifier.doi http://dx.doi.org/10.1038/npp.2013.157
• dc.identifier.issn 0893-133Xca
• dc.identifier.uri http://hdl.handle.net/10230/23333
• dc.language.iso engca
• dc.publisher Nature Publishing Groupca
• dc.relation.ispartof Neuropsychopharmacology. 2013 Nov;38(12):2515-24
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-23420
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2009-10689
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29864
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/PSI2011-24762
• dc.rights © Nature Publishing Group. http://dx.doi.org/10.1038/npp.2013.157ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Cannabinoides -- Receptors
• dc.subject.other Recompensa (Psicologia)
• dc.subject.other Nicotina
• dc.title Role of CB2 cannabinoid receptors in the rewarding, reinforcing, and physical effects of nicotineca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/acceptedVersionca