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