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Immunohistochemical analysis showed expression of Cre recombinase in the TMN of cKO mice. The reduction of histamine contents with the decreased Hdc expression in cKO brain was also confirmed. Behavioural studies revealed that chronic histamine depletion in cKO mice induced depression-like behaviour, decreased locomotor activity in the home cage, and impaired aversive memory. Sleep analysis showed that cKO mice exhibited a decrease in wakefulness and increase in non-rapid eye movement sleep throughout the day. Taken together, this study