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    Role of the 5-HT1A receptors in the effect of Galanin(1-15) on Fluoxetine-mediated action in the forced swimming test

    • Autor
      Flores-Burgess, AntonioAutoridad Universidad de Málaga; Santín-Núñez, Luis JavierAutoridad Universidad de Málaga; Díaz-Cabiale, ZaidaAutoridad Universidad de Málaga; Millón-Peñuela, CarmeloAutoridad Universidad de Málaga; Narváez-Peláez, ManuelAutoridad Universidad de Málaga; Borroto Escuela, Dasiel Óscar; Narváez-Bueno, José ÁngelAutoridad Universidad de Málaga; Fuxe, Kjell
    • Fecha
      2018-06-28
    • Palabras clave
      Biomedicina - Congresos
    • Resumen
      Galanin N-terminal fragment (1-15) [GAL(1-15)] modulates the antidepressant effects induced by the 5-HT1A receptor (5-HT1AR) agonist in the forced swimming test (FST) and the binding characteristics and mRNA levels of 5-HT1AR in the dorsal hippocampus and dorsal raphe (DR). Recently, we observed that GAL(1-15) enhanced the antidepressant-like effects induced by Fluoxetine (FLX) in the FST. In this work, we have studied whether the effects of GAL(1–15) on FLX action were mediated via 5-HT1AR, analyzing the effect of the 5-HT1AR antagonist WAY100635 in this effect and if the binding characteristics and mRNA levels of 5-HT1AR in the DR and dorsal hippocampus are modified by GAL(1-15)+FLX. Groups of rats (n=6-8) received three injections of sc FLX(10mg/kg) and 15 minutes before the FST a single icv injection of GAL(1-15) (1nmol) and 5HT1AR antagonist WAY100635(6nmol) icv alone or in combination. We also analyzed the effects of GAL(1-15)+FLX in the binding characteristics of the 5-HT1AR agonist [H3]-8-OH-DPAT and 5-HT1A mRNA levels in the DR, CA1 and Dentate Gyrus (DG). WAY100635 significantly blocked the reduction in immobility time (p<0.05), and the increase in swimming time (p<0.01) induced by GAL(1-15)+FLX in the FST. GAL(1-15)+FLX produced a significant increase in the 5HT1AR mRNA levels in CA1 (p<0.05) and DG (p<0.05). This effect was not observed in the DR. Moreover, GAL(1-15)+FLX produced a significant decrease in the Kd value (p<0.01) and in the Bmax value (p<0.05) of [3H]-8-OH-DPAT in the DG. These effects were not observed in the CA1 or in the DR. These results indicate that 5HT1AR participates in the GAL(1-15)/FLX interactions in the FST and the mechanism underlying affected the binding characteristics and the mRNA levels of 5-HT1AR specifically in the dorsal hippocampus. The heteroreceptor 5-HT1AR-GALR1-GALR2 located in the dorsal hippocampus may be the target for GAL(1-15). This work was supported by SAF2016-79008-P; PSI2013-44901-P.
    • URI
      https://hdl.handle.net/10630/16070
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    Ficheros
    CINP 2018.pdf (50.91Kb)
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    REPOSITORIO INSTITUCIONAL UNIVERSIDAD DE MÁLAGA
    REPOSITORIO INSTITUCIONAL UNIVERSIDAD DE MÁLAGA