New lessons from knockout mice: The role of serotonin during development and its possible contribution to the origins of neuropsychiatric disorders

Serotonin (5-HT) modulates numerous processes in the central nervous system that are relevant to neuropsychiatric function and dysfunction, It exerts significant effects on anxiety, mood, impulsivity, sleep, ingestive behaviors, reward system, and psychosis. Serotonergic dysfunction, has been implicated in several neuropsychiatric conditions but efforts to more clearly understand the mechanisms of this influence have been hampered by the complexity of this system at the receptor level. There are at least 14 distinct receptors that mediate the effects of 5-HT as well as several enzymes that control its synthesis and metabolism. Pharmacologic agents that target specific receptors hate provided clues regarding the function of these receptors in the adult brain. 5-HT is also an important modulator of neural development and several groups have employed a genetic strategy to ablate specific components of the 5,HT system m order to understand the role of different serotonergic in development of brain system relevant to behavior. Several inactivation mutations of specific 5-HT receptors have been generated producing interesting behavioral phenotypes related to anxiety, depression, drug abut psychosis, and cognition. In many cases, knockout mice have been used to confirm what has already been suspected based on pharmacologic studies. In other instances, mutations have demonstrated new functions of serotonergic genes in development and behavior.