Homeostatic maintenance regulated by hypothalamic neuronal histamine.

By manipulating hypothalamic neuronal histamine, its effects on brain functions related to homeostatic energy balance were assessed in non-obese normal and genetically obese Zucker rats. Feeding behavior was suppressed and drinking was accelerated by either activation of H1 receptors or inhibition of H3 receptors in the ventromedial hypothalamic nucleus (VMH) and the paraventricular nucleus, each of which is a satiety center. Energy deficiency in the brain, i.e., intraneuronal glucoprivation, produced satiation through histaminergic activation of VMH neurons. Such low energy intake in turn induced glycogenolysis in the astrocytes to protect energy deficit in the brain. Histamine neurons in the mesencephalic trigeminal nucleus (Me5) regulated masticatory functions, particularly eating speed, and those in the VMH controlled intake volume at meals. Hypothalamic histamine neurons were activated by high ambient temperature and also by interleukin-1beta, an endogenous pyrogen, through prostaglandin E2 to maintain homeostatic thermoregulation. Behavioral and metabolic abnormalities of obese Zuckers were the result of a defect in hypothalamic neuronal histamine. Abnormalities produced by depletion of neuronal histamine from the normal hypothalamus mimicked those of obese Zuckers. Grafting the lean fetal hypothalamus into the obese pups attenuated those abnormalities.