With gene targeting, one can practically knock out a gene in vivo and create a mutant organism that completely lacks the gene product. The mutant mice lacking histamine H1 receptors was generated by the method of gene targeting. In brains of homozygous mutant mice, no specific binding of [3H]pyrilamine was seen. The mutant mice showed impaired locomotor activity and exploratory behavior in an open field and activity wheel. Behaviors of the mutant mice were examined with several other tasks such as passive avoidance test, resident-intruder aggression test and formalin test to clarify the role for the H1 receptors in behaviors. Behavioral changes observed in the mutant mice are almost compatible with those obtained by the classical pharmacological tools. In correlation to the behavioral changes in the mutant mice, 5-hydroxytryptamine release was significantly increased in the brains of mutant mice.
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