Nausea and vomiting are biological systems for defense against food poisoning that are also provoked by numerous drugs
(e.g., chemotherapy, anesthesia) and chronic diseases (e.g., cancer, diabetic gastroparesis). The sensory pathways that stimulate nausea
and vomiting include vestibular, area postrema, and forebrain inputs, but gastrointestinal vagal afferent fibers arguably play the most
prominent role as a first-line defense. Vagal sensory neurons detect toxins that enter the gastrointestinal lumen and transmit information
to the hindbrain, leading to nausea (an unconditioned stimulus that serves to facilitate the avoidance of offending foods) and vomiting (a
mechanism to clear contents from the stomach). Despite the major importance of these systems to human physiology, progress on the
biological basis of nausea and vomiting has been slow – partly because laboratory rats and mice, which represent the largest thrust of
preclinical biomedical research, lack a vomiting reflex (although they appear to have indices of nausea, e.g., conditioned food aversion).
Several established models are a mainstay of preclinical nausea and vomiting research in academia and pharmaceutical companies, including
the dog, cat, ferret, and musk shrew. An argument is made for broader testing across species since each model possesses often
unique experimental advantages and sensitivity to emetic and antiemetic agents. This review focuses on the state of knowledge on the
neural pathways for nausea and vomiting, behavioral indices of nausea used in preclinical models, role of vagal afferent fibers, current
antiemetic and antinausea treatments, and potential future directions.