NEURONAL HISTAMINE IN THE HYPOTHALAMUS SUPPRESSES FOOD-INTAKE IN RATS

Using probes to manipulate hypothalamic neuronal histamine, we report here that changes in neuronal histamine modulate physiological feeding behavior in rats. Infusion of alpha-fluoromethylhistidine (FMH), a '' suicide'' inhibitor of histidine decarboxylase (HDC), into the third c erebroventricle induced feeding in the early light phase when the hist amine synthesis was most accelerated. FMH at an optimum 2.24 mumol dos e elicited feeding in 100% of rats. Treatment of FMH specifically and selectively decreased concentration of histamine without affecting con centrations of catecholamines in the hypothalamus. Immediately before the dark phase, when the histamine synthesis was normally lower, FMH i nfusion did not affect feeding-related parameters such as meal size, m eal duration or latency to eat. Conversely, thioperamide, which facili tates both synthesis and release of neuronal histamine by blocking pre synaptic autoinhibitory H-3 receptors, significantly decreased food in take after infusion of a 100-nmol dose into the third cerebroventricle . The effect of thioperamide was abolished with i.p. injection of 26 m umol/kg chlorpheniramine, an H-1 antagonist. FMH al 224 nmol was micro infused bilaterally into the feeding-related nuclei in the hypothalamu s. The ventromedial nucleus (VMH) and the paraventricular nucleus (PVN ), but not the lateral hypothalamus, the dorsomedial hypothalamus or t he preoptic anterior hypothalamus were identified as the active sites for the modulation. Neuronal histamine may convey suppressive signals of food intake through H-1 receptors in the VMH and the PVN with diurn al fluctuation.