Evidence from knockout mice that peptide YY and neuropeptide Y enforce murine locomotion, exploration and ingestive behaviour in a circadian cycle- and gender-dependent manner.

Peptide YY (PYY) and neuropeptide Y (NPY) have been proposed to participate in the control of energy homeostasis. Since these activities show circadian variations, we explored the circadian pattern of locomotor, exploratory and ingestive behaviour in male and/or female mice with disrupted genes for PYY (PYY-/-), NPY (NPY-/-) as well as PYY plus NPY (PYY+NPY-/-). The effect of bacterial lipopolysaccharide (LPS, 0.1 mg/kg intraperitoneally) on these behaviours was also examined. The animals were housed singly in cages fitted with sensors for water and food intake and two infrared frames for recording ambulation and rearing under a 12 h light/dark cycle for 4 days. Locomotor and exploratory behaviour was decreased in female NPY-/- as well as male and female PYY+NPY-/- mice during the photo- and scotophase, and in male PYY-/- mice during the scotophase. Significant decreases in water and food intake were seen in female NPY-/- as well as male and female PYY+NPY-/- mice during the photophase. The effect of LPS to attenuate ingestive behaviour during the light and/or dark phase was most pronounced in PYY-/- and NPY-/- mice. These findings attest to a circadian cycle- and gender-related role of NPY and PYY in the control of behaviours that balance energy intake and energy expenditure. Both peptides stimulate feeding and drinking to balance the energy demand that they generate by enforcing the circadian pattern of locomotion and exploration. In addition, they counteract the anorectic and antidipsogenic effects of immune challenge.