Behavioural characterization and amounts of brain monoamines and their metabolites in mice lacking histamine H1 receptors
Section snippets
Animals
The mutant mice lacking the H1 receptor subtype were generated by homologous recombination as previously described.[14]Male mutant mice (−/−) and wild-type mice (+/+) weighing 30–35 g were used. These mice were bred in our laboratory. Approximately 10 mice were housed as a group in one cage. All experiments were performed on mice at the age of three- to five-months-old. The total number of mice used in the study was 129 (+/+ mice) and 144 (−/− mice). For each behavioural task, naı̈ve mice were
Locomotor activity and motor co-ordination
The locomotion in an open field was measured in the daytime as shown in Fig. 1A. The locomotor activity of the mutant mice decreased in an open field. The decrease in locomotion was statistically significant when compared to the wild-type mice (ANOVA for nested design of time-series repeated measurement data, P<0.05). Actually, the mutant mice almost did not move at all after about 40 min in a new circumstance. The locomotor activity on the activity wheel was also measured during 24 h for five
Discussion
Decades of research have resulted in a coherent picture of the involvement of histamine in neuronal communication. In addition, the design of an increasing number of pharmacological tools to selectively modify histaminergic transmission and their utilization in electrophysiological, neurochemical, behavioural, and neuroendocrinological studies has led to a progressively more precise hypothesis about the function of the histaminergic neuron system in the CNS. An alternative approach to determine
Conclusions
Gene targeting in embryonic stem cells can produce mice with alterations to specific endogenous genes. The field has developed rapidly over the past several years, so that large numbers of mice with different gene deficiencies have been generated to study the functional roles of the gene. Here we have attempted to reveal the functional role for histamine H1 receptor-mediated neurotransmission using a new technology of gene targeting. The data obtained by this study are partly compatible with
Acknowledgements
This work was supported by grants-in-aid from the Ministry of Education, Science and Culture, the Uehara Memorial Foundation, the Sasagawa Memorial Foundation, and the Shimazu Science Foundation. We appreciate technical assistance of A. Miyake, and N. Miyama in behavioural studies. We also thank Dr I. Sato (Miyagi Cancer Center) for his suggestion of statistical evaluation.
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