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    Postsynaptic 5-HT1A receptors and regulation of body temperature in mice (2016)

    Art
    Poster
    Autoren
    Feja, Malte (WE 14)
    Noto, Bettina (WE 14)
    Fink, Heidrun (WE 14)
    Dietze, Silke (WE 14)
    Kongress
    German Pharm-Tox Summit 2016
    Berlin, 29.02. – 03.03.2016
    Quelle
    Naunyn-Schmiedeberg´s Archives of Pharmacology; 389(Suppl. 1) — S. 25
    ISSN: 0028-1298
    Sprache
    Englisch
    Verweise
    URL (Volltext): http://link.springer.com/article/10.1007%2Fs00210-016-1213-y
    DOI: 10.1007/s00210-016-1213-y
    Kontakt
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    +49 30 838 53221
    pharmakologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Objective: 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, the objective of the present study was to substantiate the contribution of postsynaptic 5-HT1A receptors to thermoregulation, more precisely to the hypothermic effect of 8-OH-DPAT, in mice.
    Methods: We used radio telemetry 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. Additionally, we investigated whether reduction of serotonergic activity by pretreatment with the 5 HT synthesis inhibitor parachlorophenylalanine (PCPA; 100 mg/kg, i. p. on four consecutive days) would alter the effects of 8-OH-DPAT on body temperature in transgenic mice postsynaptically overexpressing the 5 HT1A receptor.
    Results: 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. PCPA pretreatment did not alter the hypothermic response to 8-OH-DPAT in mice.
    Conclusions: The dose-response curves indicate a higher potency of 8-OH-DPAT in transgenic mice. The exaggerated hypothermic response to 8-OH-DPAT in mutant mice implies that postsynaptic 5 HT1A receptors could be involved in thermoregulatory function in mice. This assumption is further confirmed by the fact that 8-OH-DPAT-evoked thermal responses were not influenced by pretreatment with PCPA, most notably in transgenic mice overexpressing 5-HT1A receptors postsynaptically.