Abnormalities in obese Zuckers: defective control of histaminergic functions

Histaminergic functions in the hypothalamus of Zucker obese rats were investigated. Blockade of postsynaptic H1-receptor after infusion of chlorpheniramine into the third cerebroventricle (ICV) failed to affect feeding in obese Zuckers, although feeding was potently elicited in Wistar King A control rats. Presynaptic increase in histamine by an H3-receptor antagonist, thioperamide, suppressed feeding in Wistar controls, but not in obese Zuckers. Under high ambient temperature, Wistar controls decreased food intake and maintained their rectal temperature normally. However, obese Zuckers and histamine depleted rats due to alpha-fluoromethyl-histidine (FMH), a specific "suicide" inhibitor of a histamine synthesizing decarboxylase enzyme (HDC), failed to show this decrease in food intake as adaptive behavior. Their rectal temperature concomitantly elevated in response to heated circumstance. ICV infusion of thioperamide increased the blood glucose level in Wistar controls, but not in obese Zuckers. The defect in all these regulatory functions found in obese Zuckers may be derived from an excessive decrease in hypothalamic histamine content due to inactivity of HDC. The histamine-depleted model sufficiently mimicked the abnormalities in obese Zuckers.