Effects of histamine H1 receptor antagonists on depressive-like behavior in diabetic mice

We previously reported that streptozotocin-induced diabetic mice showed depressive-like behavior in the tail suspension test. It is well known that the central histaminergic system regulates many physiological functions including emotional behaviors. In this study, we examined the role of the central histaminergic system in the diabetes-induced depressive-like behavior in the mouse tail suspension test. The histamine contents in the hypothalamus were significantly higher in diabetic mice than in non-diabetic mice. The histamine H1 receptor antagonist chlorpheniramine (1–10 mg/kg, s.c.) dose-dependently and significantly reduced the duration of immobility in both non-diabetic and diabetic mice. In contrast, the selective histamine H1 receptor antagonists epinastine (0.03–0.3 μg/mouse, i.c.v.) and cetirizine (0.01–0.1 μg/mouse, i.c.v.) dose-dependently and significantly suppressed the duration of immobility in diabetic mice, but not in non-diabetic mice. Spontaneous locomotor activity was not affected by histamine H1 receptor antagonists in either non-diabetic or diabetic mice. In addition, the number and affinity of histamine H1 receptors in the frontal cortex were not affected by diabetes. In conclusion, we suggest that the altered neuronal system mediated by the activation of histamine H1 receptors is involved, at least in part, in the depressive-like behavior seen in diabetic mice.