Fachbereich Veterinärmedizin



    Postsynaptic 5-HT1A receptors and regulation of body temperature in mice (2015)

    Feja, Malte (WE 14)
    Noto, Bettina (WE 14)
    Fink, Heidrun (WE 14)
    Dietze, Silke (WE 14)
    25. VetPharm Symposium
    Hannover, Deutschland, 01. – 02.10.2015
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    +49 30 838 53221

    Abstract / Zusammenfassung

    Thermoregulation is a vital function in both humans and animals with the serotonin (5-HT) system, in particular the 5-HT1A receptor, playing a major role. Activating 5-HT1A receptors by the 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) leads to reduced body temperature. While there is consensus that hypothermia is induced by the stimulation of postsynaptic 5-HT1A receptors in rats and humans, the regulatory mechanisms in mice are less clear. In our group, within phenotyping a transgenic mouse line permanently overexpressing the 5-HT1A receptor in serotonergic projection areas, Bert et al. (2008, PMID: 18396339) revealed exaggerated 8-OH-DPAT-provoked hypothermic response.
    Thus, in the present study, we used radio telemetry as a non-invasive technique to monitor the basal body temperature and the hypothermic effect of different doses of 8-OH-DPAT (0.1 mg/kg – 4 mg/kg i. p.) in male transgenic mice in comparison to NMRI wild-type males. 5-HT1A overexpressing mice revealed lower levels of basal body temperature than wild types (transgenic mice: 36.0 °C; NMRI wild-type mice: 37.4 °C). In both genotypes, systemic administration of 8-OH-DPAT dose-dependently decreased body temperature, being significantly more pronounced in mutant mice (-2.8 °C compared to -1.5 °C in NMRI wild types). Dose response curves of 8-OH-DPAT revealed an ED50 = 0.4 mg/kg in transgenic and an ED50 = 0.57 mg/kg in NMRI wild-type mice, pointing towards an involvement of the postsynaptic 5-HT1A receptor in the regulation of body temperature in mice.
    Additionally, we investigated whether reduction of serotonergic activity by pretreatment with the 5 HT synthesis inhibitor parachlorophenylalanine (PCPA) would alter the effects of 8-OH-DPAT on body temperature in transgenic mice postsynaptically overexpressing the 5 HT1A receptor. The fact that 8-OH-DPAT-evoked thermal responses were not influenced by pretreatment with PCPA further substantiates a contribution of postsynaptic 5-HT1A receptors to thermoregulation in mice.