The serotonin 1A (5-hydroxytryptamine) receptor gene codes for the 5-HT1A receptor. It is expressed both presynaptically in serotonergic cell bodies and in dendrites of the dorsal raphe nucleus and postsynaptically in hippocampus. Serotonin plays a key role in many physiological and behavioral functions, including intolerance to delay, aggressivity, impulsivity, appetite, and control of temperature and sleep. Serotonergic activity is regulated, in part, by binding of serotonin to the 5-HT1A receptor. To define the mechanisms controlling 5-HT1A receptor gene expression, we isolated several overlapping genomic clones from a human genomic library and are constructing gene fusions. Allelic variants of the 5-HT1A gene have been identified by SSCP analysis in both humans and monkeys. Two polymorphisms change the protein sequence of the 5-HT1A receptor and a third is silent. In addition, an allelic variant has been identified in the 5-HT1A gene in vervet monkeys. We are studying the relationship of the human polymorphisms to impulsive behavior in alcoholic Finn violent offenders and in several other human populations and the vervet polymorphism to CSF 5-HIAA and prosocial behaviors.
