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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.
Insights
Thiamine deficiency in rats induced mouse-killing behavior (muricide). L-histidine suppressed this behavior, but its effects were reduced by inhibiting histamine synthesis, suggesting the central histaminergic system is not involved.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Nutritional Neuroscience
Background:
- Thiamine deficiency is linked to behavioral changes, including aggression.
- Mouse-killing behavior (muricide) is a complex behavior observed in rodents.
- The role of the central histaminergic system in thiamine deficiency-induced behaviors is not fully understood.
Purpose of the Study:
- To investigate the effect of L-histidine, a histamine precursor, on thiamine deficiency-induced muricide in rats.
- To explore the involvement of the central histaminergic system in this behavior.
- To assess the behavioral toxicity of L-histidine administration.
Main Methods:
- Male Wistar rats were fed a thiamine-deficient diet.
- Mouse-killing behavior was assessed.
- L-histidine was administered intraperitoneally (ip) at varying doses.
- Behavioral toxicity was evaluated using the rotarod test.
- Histidine decarboxylase was inhibited using alpha-fluoromethylhistidine (alpha FMH).
Main Results:
- Thiamine deficiency induced muricide in 70% of rats by day 30.
- L-histidine dose-dependently suppressed muricide, with an ED50 of 155 mg/kg.
- L-histidine showed minimal behavioral toxicity on the rotarod test.
- Inhibition of histamine synthesis with alpha FMH reduced the suppressive effect of L-histidine on muricide.
- Alpha-fluoromethylhistidine alone also suppressed muricide.
Conclusions:
- Both activation (L-histidine) and inhibition (alpha FMH) of the central histaminergic system suppressed thiamine deficiency-induced muricide.
- These findings suggest that muricide induced by thiamine deficiency is not mediated by the central histaminergic system.
- The study highlights a complex interaction between thiamine, histamine, and aggressive behavior.