Muricidal suppression by histidine and its antagonism by alpha-fluoromethylhistidine in thiamine deficient rats

Abstract

Male Wistar rats maintained on a thiamine deficient diet showed mouse-killing behavior (muricide). On the 30th day of experimental feeding, the incidence of muricide was 70%. Intraperitoneal (ip) injection of L-histidine, a precursor of brain histamine, suppressed the muricide induced by thiamine deficiency in a dose dependent manner. The ED50 for muricidal suppression by histidine alone was 155 mg/kg (95% confidence limits; 107.6-223.2 mg/kg). Rotarod performance was concurrently examined as an index of behavioral toxicity. High doses of histidine produced insignificant changes in rotarod performance except at 30 min after administration. Histidine exhibited a specific inhibitory activity on the muricide induced by thiamine deficiency. Pretreatment with alpha-fluoromethylhistidine (alpha FMH), a potent and specific inhibitor of histidine decarboxylase, produced a reduction in the effects of histidine. The ED50 was 400 mg/kg ip (95% confidence limits; 169.5-944 mg/kg) by histidine in combination with alpha FMH 50 mg/kg ip. However, alpha FMH also exhibited specific inhibitory activity on muricide. Either activation or inhibition of the central histaminergic system resulted in muricidal suppression in thiamine deficient rats. These data support the view that muricide induced by thiamine deficiency is not mediated by the central histaminergic system.