The molecular biology, genetics, expression pattern, and function of the 5-HT3 receptor have been extensively characterized. 5-HT3 receptors are transmitter-gated, cation selective ion channels that mediate neuronal depolarization and neurotransmitter release in both the CNS and peripheral nervous system. This receptor is targeted by antiemetic drugs during chemotherapy and anesthesia, and is also considered a potential target for treatment of gastrointestinal disorders, anxiety, and pain [32]. Although the data are far less clear and compelling, 5-HT3 receptor antagonists have also been speculatively considered for treatment of addiction [43,44]. 5-HT3 receptors modulate the activity of the mesolimbic system, which are heavily implicated in addiction to multiple substances [45]. Animal studies provide data indicating that 5-HT3 receptors could be involved in addiction and withdrawal. Mice deficient in the Htr3a gene display diminished sensitization to cocaine, a commonly used laboratory model for cocaine addiction [46]. Ondansetron reduced the CPP induced by morphine in rodents, which is a measure of the use-reinforcing properties of a drug [47], and reduced place aversion, a measure of unpleasantness during naloxone-precipitated opioid withdrawal [48]. Ondansetron reduced naloxone-precipitated withdrawal
