Sex-dependent control of murine emotional-affective behaviour in health and colitis by peptide YY and neuropeptide Y

BACKGROUND AND PURPOSE Peptide YY (PYY) and neuropeptide Y (NPY) are involved in regulating gut and brain function. Because gastrointestinal inflammation is known to enhance anxiety, we explored whether experimental colitis interacts with genetic deletion (knockout) of PYY and NPY to alter emotional-affective behaviour. EXPERIMENTAL APPROACH Male and female wild-type, NPY (NPY-/-), PYY (PYY-/-) and NPY-/-; PYY-/- double knockout mice were studied in the absence and presence of mild colitis induced by ingestion of dextran sulphate sodium (2%) in drinking water. Anxiety-like behaviour was tested on the elevated plus maze and open field, and depression-like behaviour assessed by the forced swim test. KEY RESULTS In the absence of colitis, anxiety-like behaviour was increased by deletion of NPY but not PYY in a test-and sex-dependent manner, while depression-like behaviour was enhanced in NPY-/- and PYY-/- mice of either sex. The severity of DSS-induced colitis, assessed by colonic myeloperoxidase content, was attenuated in NPY-/- but not PYY-/- mice. Colitis modified anxiety- and depression-related behaviour in a sex-, genotype-and test-related manner, and knockout experiments indicated that NPY and PYY were involved in some of these behavioural effects of colitis. CONCLUSIONS AND IMPLICATIONS These data demonstrate sex-dependent roles of NPY and PYY in regulation of anxiety-and depression-like behaviour in the absence and presence of colitis. Like NPY, the gut hormone PYY has the potential to attenuate depression-like behaviour but does not share the ability of NPY to reduce anxiety-like behaviour.