Changes in motoric, exploratory and emotional behaviours and neuronal acetylcholine content and 5‐HT turnover in histidine decarboxylase‐KO mice

Abstract

Histamine has been implicated, inter alia, in mechanisms underlying arousal, exploratory behaviour and emotionality. Here, we investigated behavioural and neurochemical parameters related to these concepts, including open-field activity, rotarod performance and anxiety, as well as brain acetylcholine and 5-HT concentrations of mice deficient for the histidine decarboxylase (HDC) gene. These mice are unable to synthesize histamine from its precursor histidine. The HDC-knockout mice showed reduced exploratory activity in an open-field, but normal habituation to a novel environment. They behaved more anxious than the controls, as assessed by the height-fear task and the graded anxiety test, a modified elevated plus-maze. Furthermore, motor coordination on the rotarod was superior to controls. Biochemical assessments revealed that the HDC-knockout mice had higher acetylcholine concentrations and a significantly higher 5-HT turnover in the frontal cortex, but reduced acetylcholine levels in the neostriatum. These results are suggestive of important interactions between neuronal histamine and these site-specific neurotransmitters, which may be related to the behavioural changes found in the HDC-deficient animals.