Increased density of brain histamine H-1 receptors in rats with portacavalanastomosis and in cirrhotic patients with chronic hepatic encephalopathy

The binding properties and the regional densities of histamine H-1 receptor s were studied in brain of rats with portacaval anastomosis (PCA) and in au topsied brain tissue from cirrhotic patients with hepatic encephalopathy (H E). Receptor binding studies and quantitative receptor autoradiography were performed, employing [H-3]mepyramine. Histamine H-1 receptors in rat brain displayed a higher density and a lower affinity compared with control huma n frontal cortex. Specific [H-3]mepyramine binding was heterogeneously dist ributed throughout the brain in both species. In human brain, binding was h ighest in the parietal and temporal cortices and lowest in caudate-putamen. In rat brain, binding was highest in the suprachiasmatic nucleus, dentate gyrus of the hippocampus, ventromedial hypothalamus, and nucleus accumbens. Cortical tissue from PCA rats and frontal cortical tissue from HE patients contained significantly increased densities (B-max) of H-1 receptors. A se lective increase in H-1 receptor density was also observed in parietal and insular cortices of HE patients. Results of the present study suggest a sel ective up-regulation of brain H-1 receptors in PCA rats and in patients wit h HE. The central histaminergic system is implicated in the control of arou sal and circadian rhythmicity. Previous studies have shown that blockade of H-1 receptors in PCA rats results in improved locomotor activity and circa dian rhythmicity scores. The present findings suggest that cortical histami nergic hyperactivity could contribute to the neuropsychiatric symptoms char acteristic of human HE, and that selective histamine H-1 receptor antagonis ts could be beneficial in the prevention and treatment of some of the sympt oms of HE in cirrhotic patients.