BEHAVIORAL CHARACTERIZATION AND AMOUNTS OF BRAIN MONOAMINES AND THEIRMETABOLITES IN MICE LACKING HISTAMINE H1 RECEPTORS

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.