Effects of oral administration of ondansetron, a 5-HT3 receptor antagonist, on anxiety-related behaviors and colonic hypercontractility in repeated stress-induced mice

Purpose

Chronic psychological stress develops and exacerbates irritable bowel syndrome (IBS). 5-hydroxytryptamine (5-HT) via activation of intestinal 5-HT₃ receptors involves impairment of intestinal functions. This study aimed to investigate the effects of ondansetron, a 5-HT₃ receptor antagonist, on locomotor activity, anxiety-related behaviors, and colonic functions in repeated water avoidance stress.

Materials and methods

Food intake and fecal pellet output (FPO) of sham stress (SS), water avoidance stress (WS), and water avoidance stress with oral administration of ondansetron (1 mg/kg BW) (WA) groups were monitored along the water avoidance stress protocol for 10 consecutive days. On day 11, locomotor activity and anxiety-related behaviors were determined using an open field test. Contractile properties of colonic tissues in response to KCl and a cumulative dose of carbachol (CCh) were determined using in vitro organ bath technique.

Results

FPO was significantly increased in the WS group after 7 days of water avoidance stress, which was reversed in WA group. WS group decreased unsupported rearing behavior compared to WS group, which was not altered in the WA group. The colon of the WS group had a higher tonic contraction in response to CCh than the SS and WA groups, which was reversed with ondansetron pre-incubation.

Conclusions

Oral administration of ondansetron prevented increased FPO but did not affect anxiety-related behavior in repeated stress model. Colonic hypercontractility in the stressed mice was related to increased responses to cholinergic-induced contractions, which involved 5-HT₃ receptors. Our findings suggest the modulatory roles of 5-HT₃ receptors to mediate stress-induced colonic dysfunction.