Brain histamine H3 receptors are predominantly presynaptic and serve an important autoregulatory function for the release of histamine and other neurotransmitters. They have been implicated in a variety of brain functions, including arousal, locomotor activity, thermoregulation, food intake, and memory. The recent cloning of the H3 receptor in our laboratory has made it possible to create a transgenic line of mice devoid of H3 receptors. This paper provides the first description of the H3 receptor-deficient mouse (H3-/-), including molecular and pharmacologic, verification of the receptor deletion as well as phenotypic screens. The H3-/- mice showed a decrease in overall locomotion, wheel-running behavior, and body temperature during the dark phase but maintained normal circadian rhythmicity. H3-/- mice were insensitive to the wake-promoting effects of the H3 receptor antagonist thioperamide. We also observed a slightly decreased stereotypic response to the dopamine releaser, methamphetamine, and an insensitivity to the amnesic effects of the cholinergic receptor antagonist, scopolamine. These data indicate that the H3 receptor-deficient mouse represents a valuable model for studying histaminergic regulation of a variety of behaviors and neurotransmitter systems, including dopamine and acetylcholine.
ASJC Scopus subject areas
- Molecular Medicine