Effects of Peripheral Administration of 5-Hydroxytryptamine (5-HT) on 2-Deoxy-D-glucose-Induced Hyperphagia in Rats.

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter and regulates several physiological functions. It is well established that 5-HT is an important factor controlling food intake and that 5-HT depresses food intake in animals and humans mediated by 5-HT receptors.1-3) Activation of central 5-HT 1B , 5-HT 2A and 5-HT 2C receptors induces anorexia in rodents based on numerous results using 5-HT receptor agonists and antagonists.1,2,4-7) Direct administration of 5-HT into the brain also induces hypophagia in rodents and its effects may be elicited by these 5-HT receptors. 3)Peripherally administered 5-HT induces anorexia and this effect may be associated with peripheral 5-HT 2 receptors, since it was antagonized by the peripheral 5-HT 2 receptor antagonist xylamidine. [8][9][10] We previously reported that the peripheral 5-HT 2 receptor agonist a-methyl-5-HT, reduces food intake in fasted rats and that it is mediated by the peripheral 5-HT 2A receptor.11) We also found that the peripheral 5-HT 3 receptor agonist 2-methyl-5-hydroxytryptamine did not affect food intake in rats, which implying that the peripheral 5-HT 3 receptor is not associated with food intake. 11)It is known that 2-deoxy-D-glucose(2-DG) prevents utilization of intracellular glucose and elicits neuroglucopenia, leading to hyperphagia. 12,13) To date, 2-DG-induced feeding serves as an animal model of hyperphagia. However, the effects of 5-HT itself on 2-DG-induced hyperphagia remain unclear. In the present study, therefore, we investigated the effects of peripheral administration of 5-HT on hyperphagia elicited by 2-DG in rats.Since 2-DG induces glucoprivation by inhibition of glucose utilization of cells, it elevates plasma glucose levels to compensate it. 12,13) 2-DG-induced hyperphagia is elicited in response to low glucose levels in the brain. It suggests that facilitation of hyperglycemia may improve shortage of glucose in the brain by increasing glucose uptake to cells, which may lead to inhibition of hyperphagia. The peripheral 5-HT receptor participates in glucose regulation. [14][15][16][17] We reported that peripheral 5-HT elicits hyperglycemia in rats.16) Thus, 5-HT may affect food intake in 2-DG-treated rats through modifying glucose levels. We also examined effects of 5-HT on blood glucose levels in 2-DG-treated rats. MATERIALS AND METHODS AnimalsMale Sprague-Dawley rats (200-240 g) were obtained from SLC Japan. They were housed in individual cages and maintained under a controlled 12 h : 12 h light/dark cycle ( lights on at 07:00 h), with room temperature at 23Ϯ 1°C and humidity at 55Ϯ5% for at least 7 d prior to experiments. Rats were given free access to food and water.Drugs and Treatment 2-DG and 5-HT creatinine sulfate were purchased from Wako Pure Chemical Co. (Japan), Merck (Germany), respectively. Ketanserin tartrate were obtained from Research Biochemicals Inc. (U.S.A.). 2-DG, 5-HT and ketanserin were dissolved in saline. All drugs were injected i.p. 2-DG and 5-HT were injected i.p. simultaneously at opposite sites. Ket...

Treatment with the 5-HT3 antagonist tropisetron modulates glucose-induced obesity in mice

“…For instance, the administration of agonists that activate the postsynaptic serotonin (5-HT) receptors has been shown to produce a marked reduction in food intake. [10][11][12] Serotonin receptor 3 (5-HT3R) is involved in the regulation of major digestive functions, such as gastric emptying and pancreatic secretion, 13,14 as well as in the control of food intake under several feeding paradigms. For instance, 5-HT3R mediates intestinal Polycose (glucose polymersFeasily digested source of carbohydrate calories) and glucose-induced suppression of food intake in short-term intraduodenal feeding models.…”