Project Summary

Laurence Tecott, M.D., Ph.D. (Independent Investigator 2001) of University of California, San Francisco, notes that while serotonin, dopamine and norepinephrine are commonly discussed as separate entities with independent functions, there is growing appreciation of the interactions of these neurotransmitter systems. It is now recognized that serotonin suppresses activity in both dopamine and norepinephrine systems. A defect in these actions of serotonin has been proposed as a possible causative factor in bipolar disorder . Because evidence implicates the serotonin 5-HT2C receptor in this dampening effect, diminished function of this receptor could lead to hyperactivity of the dopamine and norepinephrine systems. Interestingly, a line of mice with a mutation of the 5-HT2C receptor gene exhibits behavioral features reminiscent of mania, including reduced behavioral inhibition, reduced sleep and hyperactivity. Dr. Tecott aims to determine the extent to which the behavioral abnormalities of these mice assemble features of mania. His team will determine whether behavioral abnormalities may be reversed by administration of lithium chloride and valproate. They will test the hypothesis that both dopamine and norepinephrine systems are hyperactive in these animals by measuring the brain levels of dopamine and norepinephrine. This work will shed light on the potential importance of serotonin/dopamine and serotonin/ norepinephrine interactions to behaviors relevant to psychiatric disease and to the effects of drugs that influence serotonin function.

Program Area: MULTIPLE FOCUS AREAS\Schizophrenia/Mood Disorders

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