Does nutrients modulate food-intake behavior? Measurement of neurotransmitters using in vivo brain microdialysis in diabetic rat.

在目前的工作中，进行了以下研究：(实验1)糖尿病动物是否像人类糖尿病患者一样存在摄食行为异常；(实验2)摄食行为异常是否会导致糖尿病大脑中神经递质释放的改变，推测这可能导致糖尿病患者对应激源的脆弱性；(实验3)在许多食物中，咖啡及其主要成分是否有效缓解压力。(实验1)WBN/KOB大鼠和KK/Ta小鼠作为自发性糖尿病动物模型，正常Wistar大鼠和C57/BL小鼠作为对照。糖尿病动物的自发活动减少。在正常和糖尿病动物中，急性应激(100分钟-束缚)引起食物和水摄入量的减少，食物和水摄入量的昼夜节律被打乱，尤其是糖尿病小鼠。(实验二)WBN…大鼠海马区5-羟色胺(5-羟色胺)和多巴胺(DA)水平用在体脑微透析法测定MORE/KOB大鼠、链脲佐菌素(STZ)诱导的糖尿病大鼠和正常Wistar大鼠。5-羟色胺水平以正常Wistar大鼠最高，其次为STZ-大鼠和WBN/KOB大鼠。WBN/KOB大鼠的5-羟色胺水平约为正常大鼠的一半，DA水平约为正常大鼠的十分之一。使用几种离子通道阻滞剂的实验表明，糖尿病突触中的离子通道功能障碍。(3)急性束缚应激使大鼠海马区5-羟色胺水平显著升高。在正常大鼠中，咖啡、咖啡因、绿原酸和生理盐水的“第二次束缚时5-羟色胺峰值/第一次束缚时5-羟色胺峰值”(应激-应激指数)分别约为37%、34%、130%和85%。这表明，喝咖啡有助于放松束缚压力，而且咖啡的这种作用可能是由于咖啡中所含的咖啡因。另一方面，在WBN大鼠中，咖啡、咖啡因和生理盐水预处理的应激反应指数分别约为45%、51%、68%和85%，提示糖尿病动物对应激源的敏感性。较少

In the present work, the following studies were undertaken : (Exp.1) Whether the abnormal behavior of food intake in diabetic animals just like human diabetic patients exists or not ; (Exp.2) Whether the abnormality of food-intake behavior will be responsible for the altered release of neurotransmitters in the diabetic brain or not, presumably permitting the frailty to stressors ; (Exp.3) Whether among many foods coffee and its main components are effective in stress-ralaxation or not. (Exp.1) WBN/Kob rat and KK/Ta mouse as spontaneously diabetic animal, and normal Wistar-rats and C57/BL mouse as thc control were used. In diabetic animals the spontaneous locomotor activity decreased. In both normal and diabetic animals, acute stress (100 min-restraint) elicited the decrease in food- and water-intake, and the circadian rhythm of food- and water-intake was disturbed especially in diabetic mice. (Exp.2) In this experiment the hippocampal levels of serotonin (5-HT) and dopamine (DA) of WBN … More /Kob rat, streptozotocin (STZ)-induced diabetic rat and normal Wistar rat were measured using in vivo brain microdialysis method. The 5-HT level in normal Wistar rat was the largest value, followed by that in STZ-rat and WBN/Kob rat in that order. The 5-HT level in WBN/Kob rat was about a half of that of the normal rat, and the DA level in WBN/Kob rat was about one-tenth of that of the normal rat. The experiment using several ion channel blockers suggested the dysfunction of ion channels in diabetic synapse. (Exp.3) Acute restraint stress led to prominent increase in the hippocampal levels of 5-HT.In normal rat, "peak 5-HT value during 2nd restraint/peak 5-HT value during 1st restraint" (stress-ralaxing index) in pretreatment of coffee, caffeine, chlorogenic acid and saline was about 37%, 34%, 130% and 85%, respectively. This suggests that the administration of coffee contributes to relaxation of restraint stress and further this effect of coffee could be due to the caffeine which is contained in the coffee. On the other hand, in WBN rat, the stress-ralaxing index in pretreatment of coffee, caffeine, and saline was about 45%, 51%, 68% and 85%, respectively, suggesting the frailty to stressors in diabetic animals. Less