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

Abstract

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.

• Authors: P B Hedlund, P E Danielson, E A Thomas, K Slanina, M J Carson, J G Sutcliffe
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 100 Issue 3 Pg. 1375-80 (Feb 04 2003) ISSN: 0027-8424 [Print] United States
• PMID: 12529502 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hypnotics and Sedatives
• Oleic Acids
• Proto-Oncogene Proteins c-fos
• Receptors, Serotonin
• Serotonin Receptor Agonists
• serotonin 7 receptor
• Serotonin
• oleylamide
• 5-carboxamidotryptamine
• Cyclic AMP

Topics

• Allosteric Site
• Animals
• Body Temperature (drug effects)
• Cyclic AMP (metabolism)
• Female
• Hypnotics and Sedatives (pharmacology)
• Hypothermia
• Male
• Mice
• Mice, Knockout
• Models, Genetic
• Oleic Acids (pharmacology)
• Promoter Regions, Genetic
• Proto-Oncogene Proteins c-fos (metabolism)
• Receptors, Serotonin (genetics, physiology)
• Serotonin (analogs & derivatives, pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Time Factors