Using hidden behavioral patterns to study nausea in a preclinical model

Abstract

Nausea is a common clinical symptom reported by many patients experiencing cytotoxic anticancer therapy, gastrointestinal disease, and postoperative recovery. Although the neurological basis of vomiting is reasonably well established, an understanding of the physiology of nausea is lacking. The primary barrier to mechanistic research on nausea is the lack of appropriate animal models. Indeed investigating the effects of anti-nausea drugs in preclinical models is diffi cult because the primary readout is suppression of vomiting. However, animals often show a behavioral profi le of sickness, associated with reduced feeding and movement, and possibly these general behavioral measures are signs of nausea. Here we applied t-pattern analysis to determine patterns of behavior associated with emesis as a potential measure of nausea. Musk shrews were used for these experiments because they have a vomiting refl ex and other laboratory animals (rats and mice) do not. Standard emetic test agents were used in Study 1, the chemotherapy agent cisplatin (intraperitoneal), and Study 2, nicotine (subcutaneous) and copper sulfate (intragastric). Emesis and other behaviors were coded and tracked from video fi les. T-pattern analysis revealed patterns of behavior associated with emesis. Long-term tests (3 days of continuous video recording) showed that eating and drinking, and other larger body movements, including rearing, grooming, and body rotation, were signifi cantly less common in cisplatin-induced emesis-related behavioral patterns in real versus randomized data. Shortterm experiments (30 min) using nicotine and copper sulfate showed no difference between male and female shrews but there were more behavioral patterns associated with nicotine compared to copper sulfate treatment. The current approach to behavioral analysis in a preclinical model for emesis using t-pattern analysis could be used to assess the effects of drugs used to control nausea and its potential correlates, including reduced feeding and changed activity levels.