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Publication : No hypothermic response to serotonin in 5-HT7 receptor knockout mice.

First Author  Hedlund PB Year  2003
Journal  Proc Natl Acad Sci U S A Volume  100
Issue  3 Pages  1375-80
PubMed ID  12529502 Mgi Jnum  J:81842
Mgi Id  MGI:2450065 Doi  10.1073/pnas.0337340100
Citation  Hedlund PB, et al. (2003) No hypothermic response to serotonin in 5-HT7 receptor knockout mice. Proc Natl Acad Sci U S A 100(3):1375-80
abstractText  With data from recently available selective antagonists for the 5-HT(7) receptor, it has been hypothesized that 5-hydroxytryptamine (5-HT)-induced hypothermia is mediated by the 5-HT(7) receptor, an effect previously attributed to other receptor subtypes. It has been established that the biologically active lipid oleamide allosterically interacts with the 5-HT(7) receptor to regulate its transmission. The most well characterized effects of oleamide administration are induction of sleep and hypothermia. Here, we demonstrate, by using mice lacking the 5-HT(7) receptor, that 5-HT-induced hypothermia is mediated by the 5-HT(7) receptor. Both 5-HT and 5-carboxamidotryptamine, a 5-HT(1) and 5-HT(7) receptor agonist, in physiological doses fail to induce hypothermia in 5-HT(7) knockout mice. In contrast, oleamide was equally effective in inducing hypothermia in mice lacking the 5-HT(7) receptors as in wild-type mice. When administered together, 5-HT and oleamide showed additive or greater than additive effects in reducing body temperature. Taken together, the results show that 5-HT-induced hypothermia is mediated by the 5-HT(7) receptor, and that oleamide may act through an independent mechanism as well as at an allosteric 5-HT(7) receptor site to regulate body temperature.
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