Fachbereich Veterinärmedizin



    Involvement of postsynaptic 5-HT1A receptor overexpression in an animal model of depression/ anxiety (2014)

    Pilar-Cuellar, F.
    Vidal, R.
    Linge, R.
    Romero, B.
    Haberzettl, R. (WE 14)
    Bert, B. (WE 14)
    Brosda, J. (WE 14)
    Fink, H. (WE 14)
    Castro, E.
    Valdizan, E. M.
    Diaz, A.
    Pazos, A.
    9th FENS Forum of Neuroscience
    Mailand, 05. – 09.07.2014
    URL (Volltext): http://fens2014.meetingxpert.net/FENS_427/poster_102567/program.aspx
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    +49 30 838 53221

    Abstract / Zusammenfassung

    Postsynaptic 5-HT1A receptors are associated to mood disorders since they appear down-regulated in the brain of suicide victims and up-regulated after antidepressant treatment. We have evaluated the influence of postsynaptic 5-HT1A receptor overexpression (OE) on behavioural and neuroplasticity changes induced by chronic administration of corticosterone (CORT; 35 µg/ml, 28 days), or by the antidepressant fluoxetine (Flx; 25 mg/kg/day, 28 days). OE mice and WT counterparts were behaviourally evaluated in anxiety/depression paradigms, and adaptive changes in different plasticity markers were also analyzed in hippocampus.

    Corticosterone treatment in OE mice produced a decreased latency to feeding (novelty suppressed feeding) (29% vs OE+veh; p<0.05), in contrast to the increase observed in WT+CORT animals (82% vs WT+veh; p<0.05). Moreover, OE+CORT did not exhibit anhedonia in the sucrose preference test. Flx treatment reduced the anxiety levels in OE mice (51% vs OE+veh; p<0.05) to WT+veh levels.

    The analysis of the plasticity marker ß-catenin presented a reduction in OE mice (40% vs WT; p<0.05), not modified by corticosterone, while CORT induced a reduction in WT+CORT (45% vs WT, p<0.05). On contrast, Flx administration in OE mice increased hippocampal ß-catenin levels (43% vs OE+veh, p<0.05), opposite to WT animals. Analysis of serum corticosterone levels indicated a 4.7 fold increase (p<0.01) in OE mice compared to WT animal.

    Our results demonstrate the implication of postsynaptic 5-HT1A in behavioural and neuroplasticity-related changes associated to increased corticosterone levels, similar to those observed in a model of depression/anxiety.

    Supported by: Ministerio de Ciencia (SAF07-61862) and Ministerio de Economía y Competitividad (SAF2011-25020).