Ketamine-induced pica behavior as nausea and vomiting involves dopamine and serotonin receptor activation in the area postrema of rats: A comparison with etomidate and pentobarbital

One of the main adverse effects of general anesthetics is postoperative nausea and vomiting, which is distressing for patients. When rats are administered emetics, they exhibit a feeding behavior to eat non-nutritive materials such as kaolin, which is defined as pica. We investigated the effects of intraperitoneal administration of the intravenous (IV) anesthetics ketamine (150 mg/kg), etomidate (20 mg/kg), and pentobarbital (32.4 mg/kg), which are operable anesthetic doses, on kaolin intake in rats. The area postrema (AP) is involved in the development of nausea and vomiting; however, the relationship between general anesthetics and the AP remains unclear. Therefore, we also examined the effects of IV anesthetics on extracellular levels of dopamine (DA) and serotonin (5-HT) in the AP of rats using brain microdialysis. Ketamine significantly increased kaolin intake 1 day, but not 2 days after administration. Etomidate also increased kaolin intake 2 days after administration, whereas pentobarbital had no effect. Ketamine significantly increased DA levels and slightly increased serotonin levels in the AP for several hours after injection, while etomidate significantly increased serotonin levels. Pentobarbital had no effect on either level. The DAD₂ receptor antagonist haloperidol completely abolished ketamine-induced pica, while the 5-HT₃ receptor antagonist ondansetron suppressed it. In contrast, these antiemetics did not affect etomidate-induced pica. Therefore, ketamine-induced pica is associated with increased levels of DA and serotonin in the AP, which activate DAD₂ and 5-HT₃ receptors. In contrast, pentobarbital does not induce pica, and etomidate-induced pica is mediated by mechanisms other than DA and serotonin neurons.