Age-dependent measures of anxiety and cognition in male histidine decarboxylase knockout (Hdc−/−) mice

Histidine decarboxylase deficient (Hdc−/−) and wild-type male mice on the C57Bl6/J background were used to determine the role of histamine in brain function. 3–5 (Y) and 12–14 (MA) month-old Hdc−/− mice showed hypoactivity and increased measures of anxiety in the open field, light–dark, elevated plus-maze, and elevated zero maze tests. Y Hdc−/− mice showed superior performance in the hidden sessions of the water maze and passive avoidance memory retention. In contrast, Y Hdc−/− mice were impaired in novel location recognition, spent less time searching in the target quadrant and more time searching in the outer zone of the water maze during the probe trials. These behaviors are likely due to increased measures of anxiety and are not found in MA Hdc−/− mice. These data support a role for histamine in anxiety and cognition and underline the importance of considering age and potential effects on measures of anxiety in the interpretation of the role of histaminergic neurotransmission in cognitive function.