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

AUTOR(ES)

Hedlund, P. B.

FONTE

The National Academy of Sciences

RESUMO

With data from recently available selective antagonists for the 5-HT7 receptor, it has been hypothesized that 5-hydroxytryptamine (5-HT)-induced hypothermia is mediated by the 5-HT7 receptor, an effect previously attributed to other receptor subtypes. It has been established that the biologically active lipid oleamide allosterically interacts with the 5-HT7 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-HT7 receptor, that 5-HT-induced hypothermia is mediated by the 5-HT7 receptor. Both 5-HT and 5-carboxamidotryptamine, a 5-HT1 and 5-HT7 receptor agonist, in physiological doses fail to induce hypothermia in 5-HT7 knockout mice. In contrast, oleamide was equally effective in inducing hypothermia in mice lacking the 5-HT7 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-HT7 receptor, and that oleamide may act through an independent mechanism as well as at an allosteric 5-HT7 receptor site to regulate body temperature.

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