Changes in motoric, exploratory and emotional behaviours and neuronal acetylcholine content and 5-HT turnover in histidine decarboxylase-KO mice.
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.
Dere
E
E
Institute of Physiological Psychology, Center for Biological and Medical Research, Heinrich-Heine-University of Düsseldorf, D-40225 Düsseldorf, Germany.
De Souza-Silva
M A
MA
Spieler
R E
RE
Lin
J S
JS
Ohtsu
H
H
Haas
H L
HL
Huston
J P
JP
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000502:physiology; D004644:Emotions / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000201:enzymology; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D006640:Histidine Decarboxylase; D000109:Acetylcholine