Effect of Y1 receptor deficiency on motor activity, exploration and anxiety

Neuropeptide Y (NPY) in the CNS plays an important regulatory role in anxiety-related responses as exogenous administration of NPY exerts an anxiolytic-like effect in rodents. This effect is believed to be mediated by the Y-1 receptor system as pharmacological modulation of this Y-1 receptor system results in an increase in anxiety. Here we present a comprehensive phenotyping strategy for characterizing Y-1 receptor knockout animals at different times of the circadian rhythm using several motor activity-, exploration-, and anxiety-related behavioural tasks including open field, elevated plus maze, light-dark, and hole board test. We show that Y-1 deficiency has an important effect on motor activity and explorative-like behaviours and that it results in marked alterations in anxiety-related behaviours. Importantly, the behavioural phenotype of the Y-1 receptor knockout mice is circadian rhythm-dependent and also influenced by Stimuli Such as restraint stress. In addition, we found evidence for increases in working memory. Taken together, these findings suggest an important role of Y-1 receptors in the regulation of motor activity, exploration, and anxiety-related behaviours. This role is also influenced by several factors such as circadian rhythm and stress exposure confirming the importance of a comprehensive strategy and of using genetic animal models in behavioural neuroscience. (c) 2005 Elsevier B.V. All rights reserved