Orejarena Serrano, María-Juliana, 1980-Lanfumey, LaurenceMaldonado, Rafael, 1961-Robledo, Patricia, 1958-2016-01-112016-01-112011Orejarena 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/S14611457100012151461-1457http://hdl.handle.net/10230/25548The 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.application/pdfeng© 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.pdfSerotoninainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1017/S1461145710001215DopamineFood intakeLocomotionMicrodialysisSR46349Binfo:eu-repo/semantics/openAccess