Modulation of feeding behavior through brain histamine Hl-receptor

为了阐明下丘脑组胺h_1受体在控制食物摄入中的生理作用，我们研究了下丘脑神经元组胺被阻断或昼夜波动情况下的摄食行为和神经元活动。组胺H_1-，而非h_2受体拮抗剂，在光照期注入大鼠第三脑室后，呈剂量相关的强诱导摄食。这种进食是通过腹内侧下丘脑（VMH）和/或室旁核（PVN）引起的。天黑前下丘脑组胺含量较低时，立即输注后激发减弱，经-氟甲基组氨酸（FMH）（一种特定的组氨酸脱羧酶自杀抑制剂）腹腔预处理后激发消失。h_1受体拮抗剂对VMH神经元的电泳特异性抑制葡萄糖反应神经元的活性。经FMH预处理后，抑制作用减弱。这些结果表明，h_1受体拮抗剂诱导的摄食是由于在VMH和PVN中，至少部分阻断了组胺受体部位的神经元组胺。

To clarify the physiological role of hypotalamic histamine H_1-receptor in control of food intake, ingestive behavior and neuronal activities were investigated under blockade or diurnal flucturation of hypothalamic neuronal histamine. Histamine H_1-, but not H_2-receptor antagonists, potently induced feeding in a dose-related manner after infusion into rat third cerebroventricle in the light period. This feeding was elicited through ventromedial hypothlamus (VMH) and/or paraventricular neucleus (PVN). Elicitation was attenuated after infusion immediately before the dark when histamine content in the hypothalamus was low and abolished after intraperitoneal pretreatment with -fluoromethylhistidine (FMH), a specific suicide inhibitor of histidine decarboxylase. Electrophoretic application of a H_1-receptor antagonist to VMH neurons specifically suppressed activities of glucose-responding neurons. The suppressive effect was also attenuated by pretreatment with FMH. These results suggest that feeding induced by H_1-receptor antagonist is due to blokade of neuronal histamine at the site of histmaine H_1-receptors, at least in part, in VMH and PVN.