Fachbereich Veterinärmedizin



    The role of the postsynaptic 5-HT1A-receptor for the regulation of body temperature:
    a radio telemetry study (2009)

    Bert, B.
    Haberzettl, R.
    Dietze, S.
    Fink, H.
    50th Annual Meeting, Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie
    Mainz, 10. – 12.03.2009
    Naunyn-Schmiedeberg´s Archives of Pharmacology; 379(Suppl. 1) — S. 16–17
    ISSN: 0028-1298
    DOI: 10.1007/s00210-009-0404-1
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    +49 30 838 53221

    Abstract / Zusammenfassung

    The serotonin1A (5-HT1A) -receptor appears somatodendritically on serotonergic neurons
    and postynaptically on subsequent neurons. So far, the functionality of both receptor
    locations for the regulation of body temperature has not been fully clarified. For men and
    rats a postsynaptic mechanism has been assumed whereas for mice presynaptic 5-
    HT1A-receptors seem to be more important for thermoregulation. At our institute exists a
    transgenic mouse line with a distinct overexpression of the 5-HT1A-receptor in cortex
    and hippocampus, both projection areas of serotonergic neurons. A previous study
    using a rectal probe has shown that male transgenic mice exhibit a slightly lower
    baseline body temperature and respond with an exaggerated hypothermic effect to the administration of the 5-HT1A-receptor agonist 8-OH-DPAT (Bert et al. 2006, Behav Brain
    Res 167:321-41), suggesting a dominant role of the postsynaptic receptor. In the
    present study we used radio telemetry to further clarify the involvement of the
    postsynaptic 5-HT1A-receptor. We investigated whether the hypothermic effect of 8-OHDPAT
    (i.p.) could be abolished by the silent 5-HT1A-receptor antagonist WAY100635
    (1 mg/kg, i.p.) in male transgenic and wild-type mice. Additionally we tested the effect of
    the selective serotonin reuptake inhibitor fluoxetine (5, 10, 20 mg/kg, i.p.) and we
    expected that the response of transgenic mice would be more pronounced. Our results
    show that in wild-type mice 1 mg/kg 8-OH-DPAT did not affect body temperature when
    measured by radio telemetry, whereas a clear hypothermic effect was previously
    observed by rectal recordings. In transgenic mice 8-OH-DPAT induced a hypothermic
    effect measured by radio telemetry, but surprisingly the double dose (1 mg/kg) was
    needed than the one used for the rectal reading (0.5 mg/kg). This hypothermic effect
    was antagonised by 1 mg/kg WAY100635. The administration of 5 mg/kg fluoxetine was
    ineffective in both genotypes. In transgenic mice 10 mg/kg fluoxetine induced
    hypothermia, whereas only 20 mg/kg were effective in wild-type mice. In summary, our
    data show that recording the body temperature in freely moving animals by radio
    telemetry might lead to different outcomes of drug effects compared to rectal readings,
    especially concerning the dose-response relationship. Additionally, the higher sensitivity
    of transgenic mice towards 8-OH-DPAT assessed by both methods and fluoxetine
    argues for an involvement of postsynaptic 5-HT1A-receptors in the regulation of body
    temperature in mice.