Delayed stress-induced differences in locomotor and depression-related behaviour in female neuropeptide-Y Y1 receptor knockout mice

Neuropeptide-Y acting through Y1 receptors reduces anxiety and stress sensitivity in rodents. In Y1 receptor knockout (Y1^−/−) mice, however, anxiety-related behaviour is altered only in a context-dependent manner. Here, we investigated whether stress causes a delayed change in the emotional-affective behaviour of female Y1^−/− mice. Locomotor and anxiety-related behaviour was assessed with the elevated plus-maze (EPM) test and depression-like behaviour with the forced swim test (FST). These behavioural tests were also used as experimental stress paradigms. Locomotion and anxiety-like behaviour did not differ between naïve control and Y1^−/− mice. One week after the FST, locomotion was reduced in control animals but unchanged in Y1^−/− mice, whereas anxiety-like behaviour remained unaltered in both genotypes. Depression-like behaviour (immobility) was identical in naïve control and Y1^{− /−} mice but, 1 week after the EPM test, was attenuated in Y1^−/− mice relative to control animals. Our data show that naïve female Y1 ^−/− mice do not grossly differ from female control animals in their locomotor and depression-like behaviour. Exposure to the stress associated with behavioural testing, however, leads to delayed genotype-dependent differences in locomotion and depression-like behaviour. These findings attest to a role of Y1 receptor signalling in the control of stress coping and/or adaptation.