Why Can't Rodents Vomit? The Answer Lies in the Stomach, Diaphragm, and Brainstem
Vomiting is unpleasant, but it serves as an important protective mechanism. When toxic substances, gastrointestinal irritation, or certain drugs threaten the body, the nervous system coordinates the esophagus, stomach, diaphragm, abdominal muscles, and respiratory muscles to expel gastric contents through the mouth. Cats, dogs, ferrets, primates, and shrews are all capable of vomiting. Laboratory mice, however, have rarely, if ever, been observed to vomit. It was therefore unclear whether this inability was peculiar to laboratory strains or represented a general characteristic of the entire order Rodentia. Researchers also did not know whether the explanation lay in the anatomy of the digestive tract or in differences in the neural circuitry responsible for generating the vomiting response.
One study expanded the comparison to species representing the three major evolutionary divisions of Rodentia. These included the house mouse (Mus musculus), Norway rat (Rattus norvegicus), Townsend's vole (Microtus townsendii), guinea pig (Cavia porcellus), mountain beaver (Aplodontia rufa), nutria (Myocastor coypus), and North American beaver (Castor canadensis). For comparison, the researchers also examined non-rodent species with a well-established vomiting reflex: the musk shrew (Suncus murinus), ferret (Mustela putorius furo), and domestic cat (Felis catus).
The experiments did more than determine whether the animals expelled material from their stomachs. The researchers investigated the vomiting mechanism at three different levels to identify where the process might break down. They first recorded the behavior of freely moving animals after treatment with emetic agents, then compared the anatomy of their esophagus, stomach, and diaphragm. Finally, to determine whether rodents retained a weak emetic reflex too subtle to detect through ordinary observation, the researchers used an in situ brainstem preparation.
In this preparation, the animals were deeply anesthetized, higher regions of the brain and selected body tissues were removed, and the original connections among the brainstem, heart, esophagus, phrenic nerve, and relevant muscles were preserved. Oxygenated artificial perfusate was continuously delivered through the aorta so that the heart and brainstem remained functional during the experiment. The researchers then stimulated brainstem pathways pharmacologically or directly activated vagal afferent fibers with electrical stimulation. At the same time, they recorded mouth opening, esophageal contractions, shoulder movements, and phrenic nerve activity to determine whether the brainstem could organize these separate responses into a coordinated emetic motor pattern. By combining behavioral, anatomical, and neurophysiological evidence, the study could distinguish between physical constraints imposed by body structure and the absence of brainstem circuitry required to initiate and coordinate vomiting.
In the freely moving behavioral tests, the researchers used three prototypical emetic agents. Apomorphine acts primarily through pathways associated with dopamine D2 receptors. Veratrine stimulates pathways involving vagal signaling, while copper sulfate irritates the gastrointestinal tract. In species capable of vomiting, such as dogs, ferrets, and shrews, these treatments commonly induce retching and vomiting within several minutes to about fifteen minutes. Yet none of the Townsend's voles, Norway rats, guinea pigs, mountain beavers, nutrias, or North American beavers displayed genuine retching or vomiting during observation periods lasting at least forty minutes.
This did not mean that the drugs had no effect. Apomorphine increased locomotor activity in Norway rats, mountain beavers, and nutrias, while veratrine also increased movement in mountain beavers. Some animals salivated, licked themselves, opened their mouths, groomed, or displayed other behavioral changes. The researchers carefully recorded subtle oral and respiratory movements and occasionally observed coughing or a forward movement of the head accompanied by mouth opening. These actions, however, lacked the continuous and coordinated pattern seen in animals capable of vomiting.
True retching commonly begins with synchronized contractions of the diaphragm and abdominal muscles. These contractions increase intra-abdominal pressure and reposition the stomach contents toward the entrance of the esophagus in preparation for expulsion. During vomiting itself, the muscles of the thorax and abdomen must contract in a precisely timed sequence, further increasing both intra-abdominal and intrathoracic pressure so that gastric contents can travel through the esophagus and leave the mouth.
The anatomical analysis showed that the bodies of rodents are indeed poorly suited for efficient vomiting. Compared with musk shrews, ferrets, and domestic cats, the rodents examined in the study generally had a smaller proportion of muscular tissue in the diaphragm and a larger central tendon region. Although the diaphragm of the North American beaver had a relatively high density, it still contained a large central tendinous region without muscle. Because retching and vomiting depend on the diaphragm's ability to generate rapid changes in pressure, a smaller effective muscular area could reduce the efficiency of these movements.
The stomachs of vomiting species also tended to have a more funnel-like geometry, which may help direct gastric contents toward the gastroesophageal junction. Rodent stomachs were less favorably shaped for channeling material into the esophagus, potentially making vomiting more difficult. These anatomical differences could hinder the process, but the most decisive evidence came from the brainstem experiments.
Using the in situ brainstem preparation, the researchers recorded mouth movements, longitudinal esophageal contractions, shoulder displacement, and phrenic nerve activity in house mice, Norway rats, and musk shrews. The phrenic nerve controls the diaphragm and therefore provides an important measure of the motor patterns involved in respiration and vomiting. The researchers stimulated relevant brainstem pathways with resiniferatoxin and also electrically stimulated vagal afferent fibers, searching for any residual emetic response that might be impossible to detect from external observation alone.
The response of the musk shrew was unmistakable. Mouth opening, esophageal contraction, shoulder movement, and bursts of phrenic nerve activity occurred together in coordinated clusters consistent with emetic episodes. House mice and Norway rats occasionally displayed isolated mouth or esophageal movements, but these events were not organized into the same coordinated temporal pattern. Their esophagi also failed to shorten substantially after vagal afferent stimulation, and their responses lacked the characteristic organization of vomiting.
These results indicate that the limitation does not lie solely in the stomach, esophagus, or diaphragm. The rodent brainstem itself also appears to lack critical neural circuitry capable of generating the complete, patterned motor response required for vomiting. Anatomical constraints may make the physical act more difficult, but the absence of coordinated brainstem output provides the strongest explanation for why rodents cannot vomit.
An inability to vomit does not necessarily mean that rodents are incapable of experiencing nausea-like states or visceral discomfort. After exposure to stimuli that cause vomiting in other animals, house mice and Norway rats can still develop conditioned taste aversion and subsequently avoid flavors associated with illness. Their hormonal responses, however, differ from those of vomiting species. In animals with an emetic reflex, exposure to emetic stimuli is often accompanied by an increase in vasopressin. Norway rats, by comparison, more commonly show elevated oxytocin with little or no increase in vasopressin. Rodents may therefore experience some form of visceral sickness, although their neuroendocrine response may not correspond completely to nausea in animals that can vomit.
This study provides strong support for the conclusion that the inability to vomit is a general characteristic of Rodentia. It also carries an important message for biomedical research. House mice and Norway rats—the animals commonly referred to simply as mice and rats in laboratory settings—are valuable models for investigating many physiological processes, but they are poorly suited for directly studying the human vomiting reflex.
Author: Shui-Ye You
References:
Eberle JAM et al. (2013). Band-like arrangement of taste-like sensory cells at the gastric groove: evidence for paracrine communication. Frontiers in Physiology.
Horn CC et al. (2013). Why Can't Rodents Vomit? A Comparative Behavioral, Anatomical, and Physiological Study. PLOS One.
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