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Differential changes in mesolimbic dopamine following contingent and non-contingent MDMA self-administration in mice

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Abstract

Rationale

There is evidence demonstrating changes in dopamine (DA) transmission in the nucleus accumbens (NAc) related to contingent versus non-contingent drug administration.

Objectives

The aim of this study was to evaluate basal and 3,4-methylenedioxymethamphetamine (MDMA)-stimulated DA levels in the NAc of mice that had previously received contingent and non-contingent infusions of MDMA. Contingent mice were trained to self-administer MDMA (0.125 mg/kg/infusion) in 2-h sessions for 10 days. Yoked mice received either MDMA at the same dose or saline. Forty-eight hours after the last MDMA or saline administration, DA levels were measured by in vivo microdialysis before and after an MDMA (10 mg/kg, i.p.) challenge. Binding of [3H]-mazindol and [3H]-citalopram was evaluated by autoradiography.

Results

Animals receiving MDMA infusions showed significantly lower basal DA levels than the yoked saline group. A reduced activation of DA was observed following MDMA in contingent mice with respect to both yoked MDMA and saline mice. No significant alterations in DA transporter or serotonin transporter were observed in the three groups of mice.

Conclusions

These results suggest that prolonged exposure to MDMA in mice produces changes in basal DA levels after drug withdrawal and a decreased neurochemical response at the level of the mesolimbic DA reward pathway that is, in part, related to instrumental learning during self-administration.

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Acknowledgments

The authors would like to thank Ms. Dulce Real and Dr. Andrea Herrera for their contribution in the microdialysis experiments and Ms. Marta Linares for her valuable assistance with histological work. This work was supported by FIS grant number PI070709 (PR), Plan Nacional Sobre Drogas 2005 (PR), NIH-NIDA (USA), Extramural research project (5 R01 DA016768), I.S. CARLOS III Redes de grupos ISCIII (RTAG03/005), Ministerio de Ciencia y Tecnología (SAF2007-64062), Generalitat de Catalunya 2005SGR00131, GENADDICT LSHM-CT-2004-05166, and PHECOMP (LSH-FP6-037669).

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Authors and Affiliations

  1. Laboratori de Neurofarmacologia, Universitat Pompeu Fabra, PRBB, Calle Dr. Aiguader, 88, 08003, Barcelona, Spain

    María Juliana Orejarena, Fernando Berrendero, Rafael Maldonado & Patricia Robledo

  2. Institut Municipal d’Investigació Mèdica, PRBB, Calle Dr. Aiguader, 88, 08003, Barcelona, Spain

    Patricia Robledo

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  1. María Juliana Orejarena
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  2. Fernando Berrendero
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  4. Patricia Robledo
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Correspondence to Rafael Maldonado or Patricia Robledo.

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Orejarena, M.J., Berrendero, F., Maldonado, R. et al. Differential changes in mesolimbic dopamine following contingent and non-contingent MDMA self-administration in mice. Psychopharmacology 205, 457–466 (2009). https://doi.org/10.1007/s00213-009-1554-z

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  • DOI: https://doi.org/10.1007/s00213-009-1554-z

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