Modulation of the histaminergic system and behaviour by α‐fluoromethylhistidine in zebrafish

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Abstract
The functional role of histamine (HA) in zebrafish brains was studied. Zebrafish did not display a clear circadian variation in brain HA levels. Loading of zebrafish with l-histidine increased HA concentration in the brain. A single injection of the histidine decarboxylase (HDC) inhibitor, α-fluoromethylhistidine (α-FMH), gave rise to a rapid reduction in zebrafish brain HA. Low HDC activity in the brain after injections verified the effect of α-FMH. A reduction in the number of histaminergic fibres but not neurones and an increased expression of HDC mRNA was evident after α-FMH. Automated behavioural analysis after α-FMH injection showed no change in swimming activity, but abnormalities were detected in exploratory behaviour examined in a circular tank. No significant behavioural changes were detected after histidine loading. The time spent for performance in the T-maze was significantly increased in the first trial 4 days after α-FMH injections, suggesting that lack of HA may impair long-term memory. The rostrodorsal telencephalon, considered to correspond to the mammalian amygdala and hippocampus in zebrafish, is densely innervated by histaminergic fibres. These results suggest that low HA decreases anxiety and/or affects learning and memory in zebrafish, possibly through mechanisms that involve the dorsal forebrain.

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