Dextran sulfate sodium-induced colitis affects emotional and social behaviour and elevates peptide YY, neuropeptide Y and corticosterone plasma levels in mice

AM Hassan, P Jain, P Holzer. Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria

Introduction: Dextran sulfate sodium (DSS) colitis and water avoidance stress (WAS) are animal models commonly used for evaluating drug candidates to manage visceral pain. Inflammatory and functional visceral pain is associated with many psychosocial disturbances such as stress, anxiety and depression. In preclinical research it is therefore important to evaluate behavioural changes associated with these animal models because these readouts may improve the face and predictive validity of the animal models. The objective of this work was to assess various dimensions of emotional and social behaviour as well as hormonal changes evoked by DSS-induced colitis and WAS, alone and in combination.

Methods: The experiments were carried out with male adult C57BL/6N mice. Four groups of mice were studied (n=15-18 per group): control mice, mice treated with DSS, mice exposed to WAS, and mice treated with DSS+WAS. DSS (2 %) was added to the drinking water for one week. In the experiments involving WAS, the animals were exposed to WAS for 1 hour daily for one week. During these treatments the disease activity score was evaluated daily. After the end of the treatments the mice were subjected to behavioural tests including the open field test, social interaction test, and tail suspension test. The presence of colonic inflammation was confirmed by colonic weight, length and myeloperoxidase (MPO) content. Colonic myeloperoxidase as well as plasma corticosterone levels, peptide (PYY) and neuropeptide Y (NPY) were measured by ELISA. The data were analysed with two way ANOVA by using IBM SPSS 20 software.

Results: DSS treatment caused a significant decrease (P<0.001) in body weight and colon length but increased colonic weight and colonic MPO, these changes remaining unaffected by WAS. DSS also significantly increased plasma corticosterone, NPY, and PYY levels (P<0.001). In the open field test, DSS reduced the time spent in the central zone (P<0.01) and the number of central zone visits (P<0.01), which is indicative of enhanced anxiety-like behaviour. While WAS alone did not affect the time spent in the central zone and the number of central zone visits, it prevented the effect of DSS to attenuate these parameters in the open field. Similarly, the time of social interaction with a novel mouse was shortened by DSS (P<0.01), but not WAS, and the effect of DSS in the social interaction test was counteracted by WAS (P<0.05). In the tail suspension test, DSS and WAS failed to alter the immobility time, while DSS increased the time spent in swinging, but decreased the time spent in curling (P<0.01).

Conclusions: DSS-induced colitis is associated with enhanced anxiety-like behaviour, decreased social interaction, a subtle change in depression-like behaviour and an increase in the plasma levels of PYY, NPY and corticosterone. The behavioural, but not hormonal effects of DSS are prevented by psychosocial stress, which attests to a complex interaction of inflammation and stress in visceral pain conditions. The DSS-evoked behavioural and hormonal responses might be used as add-on readouts in evaluating the activity of drug candidates on visceral pain.