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Effect of alpha-fluoromethylhistidine on brain histamine and noradrenaline in muricidal rats
K Onodera1, A Yamatodani, T Watanabe
1Department of Pharmacology, Tohoku University School of Dentistry, Sendai, Japan.
Abstract:
Rats maintained on a thiamine-deficient diet for 30 days showed mouse-killing aggression (muricide). Once the muricide tendency appeared, it remained during the entire experimental period, even after subsequent administration of thiamine hydrochloride for 30 days. The effect of alpha-fluoromethylhistidine (FMH) on muricide in this animal model was examined, and histamine and noradrenaline levels in several brain regions were measured. One hour after i.p. injection of 200 mg/kg of FMH, muricide was completely abolished. Significant decrease in histamine levels was found in the hypothalamus, thalamus, amygdala, striatum and pituitary of muricidal rats. Thus, the central histaminergic neuron system may be involved in the suppressive mechanism of muricide. On the other hand, it is noteworthy that the noradrenaline level was significantly decreased only in the hypothalamus. In conclusion, it seems likely that the suppression of muricide induced by FMH was attributable to both inhibition of the histaminergic system and activation of the noradrenergic system.
Insights
Thiamine deficiency in rats induced mouse-killing behavior (muricide). Alpha-fluoromethylhistidine (FMH) abolished muricide by affecting central neurotransmitter systems, specifically histamine and noradrenaline.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Pharmacology
Background:
- Thiamine deficiency in rats is a known cause of mouse-killing aggression (muricide).
- This aggressive behavior persists even after thiamine repletion.
- The underlying neurochemical mechanisms of muricide remain incompletely understood.
Purpose of the Study:
- To investigate the effects of alpha-fluoromethylhistidine (FMH) on muricide in a thiamine-deficient rat model.
- To examine the changes in brain histamine and noradrenaline levels following FMH administration in muricidal rats.
Main Methods:
- Rats were fed a thiamine-deficient diet for 30 days to induce muricide.
- Alpha-fluoromethylhistidine (FMH) was administered intraperitoneally (i.p.) at a dose of 200 mg/kg.
- Histamine and noradrenaline levels were measured in various brain regions (hypothalamus, thalamus, amygdala, striatum, pituitary) using biochemical assays.
Main Results:
- FMH administration (200 mg/kg, i.p.) completely suppressed muricide in rats within one hour.
- Muricidal rats showed significantly decreased histamine levels in the hypothalamus, thalamus, amygdala, striatum, and pituitary.
- A significant decrease in noradrenaline levels was observed only in the hypothalamus of muricidal rats.
Conclusions:
- The central histaminergic system plays a crucial role in the regulation of muricide.
- FMH-induced suppression of muricide likely involves the inhibition of the histaminergic system.
- The findings suggest a potential dual mechanism involving histaminergic inhibition and noradrenergic activation in FMH's effect on muricide.