Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviour

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Orejarena Serrano, María-Juliana, 1980-ca
  • dc.contributor.author Lanfumey, Laurenceca
  • dc.contributor.author Maldonado, Rafael, 1961-ca
  • dc.contributor.author Robledo, Patricia, 1958-ca
  • dc.date.accessioned 2016-01-11T14:00:56Z
  • dc.date.available 2016-01-11T14:00:56Z
  • dc.date.issued 2011
  • dc.description.abstract The serotonergic system appears crucial for (±)-3,4-methylenedioxymethamphetamine (MDMA) reinforcing properties. Current evidence indicates that serotonin 5-HT2A receptors (5-HT2ARs) modulate mesolimbic dopamine (DA) activity and several behavioural responses related to the addictive properties of psychostimulants. This study evaluated the role of 5-HT2ARs in MDMA-induced reinforcement and hyperlocomotion, and the reinstatement of MDMA-seeking behaviour. Basal and MDMA-stimulated extracellular levels of DA in the nucleus accumbens (NAc) and serotonin and noradrenaline in the prefrontal cortex were also assessed. Self-administration of MDMA was blunted in 5-HT2AR knockout (KO) mice compared to wild-type (WT) littermates at both doses tested (0.125 and 0.25 mg/kg per infusion). Horizontal locomotion was increased by MDMA (10 and 20 mg/kg i.p.) to a higher extent in KO than in WT mice. DA outflow in the NAc was lower in KO compared to WT mice under basal conditions and after MDMA (20 mg/kg) challenge. In WT mice, MDMA (5 and 10 mg/kg i.p.) priming did not reinstate MDMA-seeking behaviour, while cue-induced reinstatement was prominent. This cue-induced reinstatement was blocked by administration of the selective 5-HT2AR antagonist, SR46349B (eplivanserin) at a dose of 0.5 mg/kg, but not at 0.25 mg/kg. Our results indicate that 5-HT2ARs are crucial for MDMA-induced reinforcement and cue-induced reinstatement of MDMA-seeking behaviour. These effects are probably due to the modulation of mesolimbic dopaminergic activity.ca
  • dc.description.sponsorship This work was supported by the Instituto de Salud Carlos III FIS grant no. PI070709 (to P.R.) and Red de trastornos adictivos (RTA-RETICS) grant no. RD06/001/001 (to R.M.), the Ministerio de Ciencia e Innovación grant no. SAF2007-64062 (to R.M.), the Generalitat de Catalunya grant no. 2009SGR00731 and ICREA Academia award (to R.M.) and the European Commission projects GENADDICT (no. LSHM-CT-2004-05166) and PHECOMP (no. LSHM-CT-037669) (both to R.M.)
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Orejarena MJ, Lanfumey L, Maldonado R, Robledo P. Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviour. Int J Neuropsychopharmacol. 2011;14(7):927-40. DOI: 10.1017/S1461145710001215ca
  • dc.identifier.doi http://dx.doi.org/10.1017/S1461145710001215
  • dc.identifier.issn 1461-1457
  • dc.identifier.uri http://hdl.handle.net/10230/25548
  • dc.language.iso engca
  • dc.publisher Cambridge University Pressca
  • dc.relation.ispartof The international journal of neuropsychopharmacology. 2011;14(7):927-40
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/5166
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/37669
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062
  • dc.rights © Cambridge University Press. The published version of the article: Orejarena MJ, Lanfumey L, Maldonado R, Robledo P. Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviour. The international journal of neuropsychopharmacology. 2011; 14(7): 927-940. DOI 10.1017/S1461145710001215 is available at http://ijnp.oxfordjournals.org/content/ijnp/14/7/927.full.pdfca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.subject.keyword Dopamine
  • dc.subject.keyword Food intake
  • dc.subject.keyword Locomotion
  • dc.subject.keyword Microdialysis
  • dc.subject.keyword SR46349B
  • dc.subject.other Serotoninaca
  • dc.title Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviourca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

Col·leccions

Articles (Departament de Medicina i Ciències de la Vida)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)