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

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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.