5-HT2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature.

Recreational drugs such as 3,4-methylenedioxymethamphetamine and cocaine induce hyperthermia, which is affected by ambient temperature. 2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe), a selective agonist of 5-HT2A receptor used as a recreational drug, reportedly induces hyperthermia. This study aimed to verify whether 25B-NBOMe induces ambient temperature-dependent hyperthermia and to clarify its mechanism. Eight-week-old male Sprague-Dawley rats were administered intraperitoneal injection of 25B-NBOMe at an ambient temperature of 23°C or 29°C. 25B-NBOMe administration at 23°C did not change the core body temperature of the rats, whereas administration at 29°C induced significant hyperthermia 30-120 minutes postadministration. Tail surface temperature temporarily decreased 30 minutes postadministration, indicating heat storage by peripheral vasoconstriction despite a high ambient temperature. Because 25B-NBOMe-induced-hyperthermia was suppressed by sarpogrelate, but not by destruction of central noradrenaline or serotonin neurons, peripheral 5-HT2A receptors were considered contributors to the development of hyperthermia at a high ambient temperature, independently from central neurons. The temperature of brown adipose tissue (BAT) increased 60-120 minutes postadministration of 25B-NBOMe at 29°C, indicating thermogenesis. Previous studies have reported that peripheral serotonin contributes to the inhibition of BAT thermogenesis. Decreased plasma serotonin levels were observed at 29°C, and serotonin administration partially suppressed 25B-NBOMe-induced hyperthermia at a high ambient temperature, suggesting that decreased levels of peripheral serotonin induced BAT thermogenesis. Our findings indicate that 25B-NBOMe induces hyperthermia at a high ambient temperature via vasoconstriction regulated by 5-HT2A receptors and BAT thermogenesis mediated by decreased levels of plasma serotonin. Thus, peripheral serotonin plays a partial but important role in thermoregulation.

Antidepressant effect of extracts from Ginkgo biloba leaves in behavioral models.

Extracts of Ginkgo biloba (EGB) are a complex product prepared from green leaves of the Ginkgo biloba tree. In the present study, the antidepressant effect of EGB was examined using two behavioral models, the forced swimming test (FST) in rats and tail suspension test (TST) in mice. EGB significantly reduced immobility time in the FST at a dosage of 10 and 50 mg/kg body weight after repeated oral treatment for 14 d, although no change of motor dysfunction was observed with the same dosage in the open field test. These results indicate that EGB might possess an antidepressant activity. In addition, EGB markedly shortened immobility time in the TST after acute inter-peritoneal treatment at a dosage of 50 and 100 mg/kg body weight. The present study clearly demonstrated that EGB exerts an antidepressant effect in these two behavioral models.