Sakata T, Ookuma K, Fujimoto K, Fukagawa K, Yoshimatsu H
Department of Internal Medicine I, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Brain Res Bull. 1991 Sep-Oct;27(3-4):371-5. doi: 10.1016/0361-9230(91)90127-6.
Manipulating neuronal histamine in the hypothalamus, its effects on brain functions were assessed in nonobese normal rats and Zucker rats. Alpha-fluoromethylhistidine (FMH), an inhibitor of histamine synthesis, induced feeding dose-dependently after 2.24 mumol infusion at 1100 h, when hypothalamic histamine was normally high. This dose of FMH selectively decreased hypothalamic histamine, but not other neurotransmitters. Thioperamide, an antagonist of autoinhibitory H3-receptors, decreased food intake after infusion at 1940 h, when hypothalamic histamine was normally low. Bilateral microinfusion of 224 nmol FMH or 26 nmol chlorpheniramine, an H1-antagonist, into the ventromedial hypothalamus (VMH) and the paraventricular nucleus (PVN), elicited feeding. However, Zucker obese rats showed no significant responses to chlorpheniramine, thioperamide or histamine. Concentration of their hypothalamic histamine was excessively lower than that of the nonobese. Contents of hypothalamic histamine were lowered at 4 degrees C and raised at 31 degrees C. FMH attenuated increase in histamine, and then disrupted adaptive behavior. These findings indicate that neuronal histamine may convey the suppressive signal of food intake through H1-receptors in the VMH and/or the PVN, and play critical roles in homeostatic control of adaptive behavior.
通过调控下丘脑神经元组胺，在非肥胖正常大鼠和 Zucker 大鼠中评估其对脑功能的影响。组胺合成抑制剂α-氟甲基组氨酸（FMH）在 1100 时输注 2.24 μmol 后，剂量依赖性地诱导进食，此时下丘脑组胺通常处于高水平。该剂量的 FMH 选择性降低下丘脑组胺，但不影响其他神经递质。自抑制性 H3 受体拮抗剂硫代哌酰胺在 1940 时输注后减少食物摄入，此时下丘脑组胺通常处于低水平。向腹内侧下丘脑（VMH）和室旁核（PVN）双侧微量注射 224 nmol FMH 或 26 nmol H1 拮抗剂氯苯那敏可引发进食。然而，Zucker 肥胖大鼠对氯苯那敏、硫代哌酰胺或组胺无明显反应。它们下丘脑组胺浓度比非肥胖大鼠低得多。下丘脑组胺含量在 4℃时降低，在 31℃时升高。FMH 减弱组胺增加，进而破坏适应性行为。这些发现表明，神经元组胺可能通过 VMH 和/或 PVN 中的 H1 受体传递食物摄入的抑制信号，并在适应性行为的稳态控制中发挥关键作用。
