Implicación del sistema serotoninérgico y dopaminérgico en los efectos reforzantes de la MDMA

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Adolescence represents a developmental period characterized by high vulnerability to drug consumption. Adolescents are the main consumers of 3,4-methylene-dioxy- methamphetamine (MDMA), an amphetamine derivate with addictive potential. The aim of the present study was to evaluate the role of serotonergic and dopaminergic systems in the rewarding and reinstating properties of MDMA, specifically the implication of these neurotransmitter systems in the acquisition, expression and reinstatement of MDMA-induced Conditioned Place Preference (CPP) in adolescent mice. For this purpose we evaluated different agonists and antagonists of these neurotransmitter systems in the abovementioned phases of CPP. In addition, we studied the effects of MDMA and the rest of pharmacological treatments on DA and 5-HT and their metabolite concentrations in cerebral tissue, as well as changes in dopamine transporter (DAT) or serotonin transporter (SERT) concentrations in the striatum during different phases of an MDMA-induced CPP. We set out to confirm the addictive power of MDMA, to evaluate whether serotonergic and dopaminergic drugs facilitate or impair an MDMA-induced CPP process and to assess their relationship with reinstatement. In general, our results suggest that the neurobiological mechanisms of acquisition, expression and reinstatement differ. Additionally, different serotonergic and dopaminergic receptor subtypes are involved in the acquisition, expression and reinstatement of an MDMA-induced CPP in adolescent mice. The serotonergic system is implicated in the acquisition, expression and reinstatement of an MDMA-induced CPP. On the other hand, the dopaminergic system is implicated in the acquisition and expression of MDMA-induced CPP, but does not seem to be critical to MDMA-induced reinstatement of a previously extinguished preference. These findings improve our understanding of the neurobiological mechanisms of the rewarding properties of MDMA, and should help to design rational pharmacological strategies for the treatment of patients who have difficulty controlling their consumption.
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