K. Yanai et al., BEHAVIORAL CHARACTERIZATION AND AMOUNTS OF BRAIN MONOAMINES AND THEIRMETABOLITES IN MICE LACKING HISTAMINE H1 RECEPTORS, Neuroscience, 87(2), 1998, pp. 479-487
Behavioural assessments were made of mutant mice lacking histamine H1
receptors to reveal the function of H1 receptors in the behaviour of m
ice. Exploratory behaviour of mice in a new environment was examined t
o discover whether the absence of H1 receptors in mice affects actions
relating to their emotions. The H1 receptor-deficient mice showed a s
ignificant decrease in ambulation in an open field and on an activity
wheel. Cognitive functions and anxiety were examined using passive avo
idance response test and the elevated plus-maze test, respectively. Th
e passive avoidance rest did not show any change in latency. The eleva
ted plus-maze test revealed that the transfer latency of the mutant mi
ce was significantly prolonged, indicating that H1 receptors are partl
y associated with the control of anxiety. Aggressive behaviour was exa
mined by a resident-intruder aggression test. When confronted with an
intruder, the mutant mice attacked the intruder significantly slower a
nd less frequently than did wild-type mice after a six-month isolation
period. A formalin test and a forced swimming test were used to evalu
ate the nociceptive response and depressive or despairing state, respe
ctively, of both groups. The mutant mice showed a significant decrease
of nociceptive response in the late phase without affecting the early
phase. There was no significant difference in the forced swimming tes
t between the two groups. The brain content of monoamines and their me
tabolites was measured in the H1 receptor null and wild-type mice. The
turnover rate of 5-hydroxytryptamine defined by the ratio of 5-hydrox
yindoleacetic acid and 5-hydroxytryptamine was significantly increased
in the cerebral cortex and hippocampus of H1 receptor null mice. Thes
e results support the previous pharmacological findings that histamine
modulates various neurophysiological functions such as locomotor acti
vity, emotion, memory and learning, nociception and aggressive behavio
ur through H1 receptors. (C) 1998 IBRO. Published by Eisevier Science
Ltd.