Behavioral Patterns Associated with Chemotherapy-Induced Emesis: A Potential Signature for Nausea in Musk Shrews

Abstract

Nausea and vomiting are common symptoms in patients with many diseases, including cancer and its treatments. Although the neurological basis of vomiting is reasonably well known, an understanding of the physiology of nausea is lacking. The primary barrier to mechanistic research on the nausea system is the lack of an animal model. Indeed investigating the effects of anti-nausea drugs in pre-clinical models is difficult because the primary readout is often emesis. It is known that animals show a behavioral profile of sickness, associated with reduced feeding and movement, and possibly these general measures are signs of nausea. Studies attempting to relate the occurrence of additional behaviors to emesis have produced mixed results. Here we applied a statistical method, temporal pattern (t-pattern) analysis, to determine patterns of behavior associated with emesis. Musk shrews were injected with the chemotherapy agent cisplatin (a gold standard in emesis research) to induce acute (<24 h) and delayed (>24 h) emesis. Emesis and other behaviors were coded and tracked from video files. T-pattern analysis revealed hundreds of non-random patterns of behavior associated with emesis, including sniffing, changes in body contraction, and locomotion. There was little evidence that locomotion was inhibited by the occurrence of emesis. Eating, drinking, and other larger body movements including rearing, grooming, and body rotation, were significantly less common in emesis-related behavioral patterns in real versus randomized data. These results lend preliminary evidence for the expression of emesis-related behavioral patterns, including reduced ingestive behavior, grooming, and exploratory behaviors. In summary, this statistical approach to behavioral analysis in a pre-clinical emesis research model could be used to assess the more global effects and limitations of drugs used to control nausea and its potential correlates, including reduced feeding and activity levels.

T-pattern analysis for the study of temporal structure of animal and human behavior: A comprehensive review

“…In two recent articles from Horn et al (2011Horn et al ( , 2013, T-pattern analysis has been applied to study emetic behavior in the Suncus Murinus, a little mammal, similar to a rodent, belonging to the family of Soricidae. It resulted that several non-random patterns of behavior are associated with emesis, including sniffing, changes in body contraction and locomotion (Horn et al, 2011).…”

“…It resulted that several non-random patterns of behavior are associated with emesis, including sniffing, changes in body contraction and locomotion (Horn et al, 2011). In addition, the use of new dynamic behavioral measures to more comprehensively evaluate emesis and the impact of therapies have been proposed (Horn et al, 2013).…”

Autonomic changes induced by provocative motion in rats bred for high (HAB) and low (LAB) anxiety-related behavior: Paradoxical responses in LAB animals

“…The initial premise of this study was that we expected that if the hypothermic response to motion is an index of a nausea-like state in rats (10,18), then as anxiety is a risk factor for nausea in humans (see Introduction), the hypothermic response to rotation in HAB rats should be greater than in LAB rats. Contrary to our expectations, the LAB animals had the largest hypothermic and bradycardia responses to motion, with no major differences between HAB and NAB.…”

“…Research on nausea (or a functionally equivalent sensation) in experimental animals is based on indirect measurements that are of arguable specificity and validity (e.g. modified behavior pattern [18,27]; reduced food consumption and gastric stasis [4,30]; pica, indicated by kaolin consumption [45,51]) or require conditioning (e.g. conditioned taste/food aversion [14,16] and conditioned gaping [38,39]).…”

Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews

“…The traditional stimulus for investigating the GI vagal afferent component of emesis is intragastric administration of copper sulfate (CuSO 4 ), a gastric irritant (25,50); however, its action in musk shrews (Suncus murinus), the primary small animal model for emesis research, is not well defined (e.g., 17,20,26,31,34,47). Furthermore, although viral tracing techniques have been used to identify brain regions that receive abdominal vagal afferent inputs in nonemetic rodents (37), parallel studies in emetic species have not been conducted.…”