Anticipatory nausea in animal models: a review of potential novel therapeutic treatments

Cancer patients undergoing chemotherapy continue to experience the debilitating side effect of nausea associated with their treatment. Although acute and delayed vomiting have become well managed with the advent of the 5-hydroxytryptamine-3 antagonists, such as ondansetron, and the neurokinin-1 receptor antagonists (such as aprepitant), nausea is still a relatively unmanaged adverse side effect of chemotherapy treatment. When nausea and vomiting are not properly managed, patients are at a greater risk of developing anticipatory nausea (AN)—a conditional association between chemotherapy-related treatment cues, such as the clinic environment, and the subsequent nausea experienced. Once it develops, AN is refractive to pharmacological treatment with classic antiemetics. Currently, non-specific antianxiety drugs (benzodiazepines) are prescribed; however, their sedating side effects are undesirable. Here, we review the animal models of AN that have been developed. These preclinical models have aided researchers in the evaluation of potentially efficacious pharmacological treatments for AN. Accumulating evidence using animal models demonstrates that cannabinoid compounds effectively reduce AN, without producing sedation. These results highlight the need for human clinical trials evaluating the efficacy of these compounds.