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Local acamprosate modulates dopamine release in the rat nucleus accumbens through NMDA receptors: an in vivo microdialysis study

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Abstract.

The effects of acamprosate on the in vivo dopamine extracellular levels in the nucleus accumbens and the involvement of N-methyl-D-aspartate (NMDA) receptors in these effects were investigated. Microdialysis in freely moving rats was used to assess dopamine levels before and during simultaneous perfusion of acamprosate and/or different agonists or antagonists of NMDA receptors. Perfusion with acamprosate at concentrations of 0.5 and 5 mM provoked a concentration-dependent increase in extracellular dopamine in nucleus accumbens. The lowest concentration of acamprosate assayed (0.05 mM) had no effect on dopamine levels. Infusion of NMDA (25 and 500 µM) and the glutamate uptake blocker, L-trans-pyrrolidine-2,4-dicarboxilic acid (PDC) (0.5 mM) into the NAc caused a significant increase in DA, whereas acamprosate (0.05 mM) co-infusion with these compounds blocked or attenuated the NMDA and PDC-induced increases in DA levels. Co-infusion of the selective antagonist of NMDA receptors, DL-2-amino-5-phosphonopentanoic acid (AP5) (400 µM) with acamprosate (0.5 mM), did not reduce the increase of DA levels induced by acamprosate. These results demonstrate that acamprosate is able to modulate DA extracellular levels in NAc via NMDA receptors and suggest that acamprosate acts as an antagonist of NMDA receptors.

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Acknowledgements.

This work was supported by funds of Delegación del Gobierno para el Plan Nacional sobre Drogas, Ministerio del Interior, Spain. TZS is a recipient of a grant from Ministerio de Educación, Cultura y Deportes, Spain. MJCC is a recipient of a grant from Delegación del Gobierno para el Plan Nacional sobre Drogas, Ministerio del Interior, Spain.

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Authors and Affiliations

  1. Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Valencia, 46100 , Burjassot, Spain

    M. J. Cano-Cebrián, T. Zornoza-Sabina, A. Polache & L. Granero

  2. Instituto de Investigaciones Citológicas (FVIB), C/ Amadeo de Saboya, 4, 46010, Valencia, Spain

    C. Guerri

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  1. M. J. Cano-Cebrián
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  2. T. Zornoza-Sabina
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  5. L. Granero
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Correspondence to L. Granero.

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Cano-Cebrián, M.J., Zornoza-Sabina, T., Guerri, C. et al. Local acamprosate modulates dopamine release in the rat nucleus accumbens through NMDA receptors: an in vivo microdialysis study. Naunyn-Schmiedeberg's Arch Pharmacol 367, 119–125 (2003). https://doi.org/10.1007/s00210-002-0674-3

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