Physiological significance of the histaminergic system : A brain microdialysis study using unanesthetized and freely-moving rats

为了阐明中枢组胺能神经元系统的生理意义及其神经化学机制，我用MIER检测了大鼠脑内内源性组胺的动态变化。卵巢透析法。接下来的。结果表明：(1)下丘脑前部的组胺释放对河豚毒素敏感，并依赖于细胞外钙离子，组胺能胞体和神经末梢的去极化刺激可增强组胺的释放，表明组胺的释放来自神经元。(2)组胺的释放有明显的昼夜变化，暗时高，光时低。(3)经透析膜给药时，GABA和谷氨酸的释放分别受到抑制和增强。进一步的神经化学研究表明，谷氨酸对内源性乙酰胆碱的释放是通过位于组胺能神经末梢的突触前NMDA受体介导的。(4)电刺激组胺能胞体所在的结节乳头核可增加内源性乙酰胆碱的释放。电诱发的乙酰胆碱释放可被组胺合成的S受体阻断剂α-氟代组氨酸或组胺H_2受体阻断剂唑替丁所抑制。硫代巴比妥钠显著增加基础乙酰胆碱释放，通过阻断突触前自身受体H3受体而增强组胺释放。这一结果表明，位于内侧隔区的胆碱能神经元的活动受组胺能系统的调节。(5)刺激前庭可增加下丘脑前部的组胺释放，提示中枢组胺能系统可能参与运动病的前庭自主神经反射。

To elucidate physiological significance and its neurochemical mechanisms of the central histaminergic neuron system, I examined dynamics of endogenous histamine in the rat brain using a mier. odialysis method. The- following. are the summary of research results.(1)Histamine release from the anterior hypothalamic area was sensitive to tetorodotoxin and dependent on extracellular calcium, and was enhanced by depolarization stimuli of the histaminergic cell bodies and nerve terminals, indicating that the observed release was of neuronal origin.(2)The release had a clear eircadian variation being high in dark period and low in light period.(3)When GABA or glutamic acid was administered through the dialysis membrane, the release was suppressed and enhanced, respectively. Further neurochemical studies revealed that the enhancement of the release by glutamic acid was mediated by presynaptic NMDA receptors located on histaminergic nerve terminals.(4)The release of endogenous acetylcholine from the hippocampus was increased by electrical stimulation on the tuberomammillary nucleus where the histaminergic cell bodies were confined. The electrically evoked acetylcholine release was suppressed by int raperitoneal administration of alpha-fluorometylhistidine, a s pe c if i c inhibitor of histamine synthesis or zolantidine, a- brain-penetrating histamine H2receptor blocker. The basal acetylcholine release was significantly increased by thioperamide administration, which enhanced the histamine release by blocking presynaptic autoreceptor, H3-receptor. This result indicates that activity of the cholinergic neurons located in the medial septum is regulated by the histaminergic system.(5)Histamine release from the anterior hypothalamic area was increased by vestibular stimulation indicating possible participation of the central histaminergic system in the vestibular-autonomic reflex of motion sickness.