Department of Pharmacology
Columbia University Medical Center
He is professsor at Columbia University.
Serotonin (5HT) is involved in a wide range of behaviors, and serotonergic drugs are used in the treatment of a number of pathological states such as depression, appetite disorders, and migraines. Pharmacological studies and molecular cloning have identified several subtypes of receptors with distinct pharmacological properties, signaling systems, and tissue distributions. The study of the function of individual serotonin receptor subtypes has been hampered by the lack of specific drugs. In addition, a number of the serotonergic drugs that are active in the treatment of neuropsychiatric disorders influence the whole serotonergic system. For example, antidepressants such as fluoxetine (Prozac) are 5-HT uptake blockers. These drugs presumably potentiate the action of 5-HT at multiple post-synaptic sites. We do not know which of these post-synaptic receptors are responsible for the antidepressant activities of 5-HT uptake blockers, however. To dissect the contributions of individual serotonin receptors to physiology and behavior, we have created mouse mutants lacking individual receptor subtypes. These mice provide genetic models for a number of human behavioral traits such as: impulsiveness, depression, and vulnerability to drugs of abuse. The neural circuits underlying these traits are currently under investigation.