TUESDAY, March 5, 2002 (HealthDayNews) -- Scientists are peering deeper than ever into the molecular mysteries of chemicals that relay messages between brain cells and control emotion.
Two different studies, one from researchers at Rockefeller University in New York and one from Eli Lilly & Co. in Indianapolis, show that a protein known as DARPP-32 plays a critical role in the effects of the neurotransmitter serotonin.
The reports, which appear in today's issue of the journal Proceedings of the National Academy of Sciences, link DARPP-32 to the effects of various drugs, including antidepressants such as Prozac and drugs of abuse such as cocaine and ecstasy. The researchers hope the findings could eventually lead to better treatments for depression.
Angus C. Nairn, a professor of psychiatry who studies DARPP-32 at Yale University, is familiar with the studies. Most of the work done in this area has focused on the neurotransmitter dopamine, which is best known for its role in Parkinson's disease, he says, but this latest research establishes a framework for studying the neurotransmitter serotonin, which is involved in emotions and depression.
"The distinction of this work is that we move into the cell and start to describe how these drugs have consequences in terms of the function of the individual neurons," Nairn says. "They're moving further downstream into the details of how these drugs have their effects."
"If we can understand the details of how [antidepressants like Prozac] work in terms of the downstream targets, then we can complement those [drugs] by learning about those new targets," he adds.
In the first study, researchers led by Dr. Per Svenningsson at Rockefeller's Laboratory of Molecular and Cellular Neuroscience report that DARPP-32 helps to regulate signaling involving serotonin in the brains and behavior of mice.
"Serotonin activates the receptors that are on the cell surface," Svenningsson says. "In turn, the receptors on the cell surface activate other proteins within the cell, and one of those proteins is DARPP-32."
In the second study, the researchers found the antidepressant Prozac, which is made by Lilly, affects the chemical state of DARPP-32 in several different regions of the mouse brain, including the prefrontal cortex, the hippocampus and the striatum.
At the same time, Svenningsson found mice bred without the gene for DARPP-32 didn't experience the same anti-depressive effect from Prozac as mice with the DARPP-32 gene did.
When Svenningsson and his colleagues bred mice lacking the ability to produce DARPP-32, they found the behavioral effects of drugs that normally cause the release of serotonin were significantly reduced.
"The function of this protein is regulated by Prozac," he says, adding he would expect to see the same effect from other drugs in Prozac's family of antidepressants, known as selective serotonin reuptake inhibitors (SSRIs).
The researchers also found that mice treated over a long period with Prozac experienced gradual increases in DARPP-32 production. "When they chronically treat these animals, they're seeing relatively slow increases in the expression of this protein called DARPP-32
with a time course that parallels the clinical efficacy [of Prozac]," he says.
This may help explain why people with depression who start to take Prozac often have to wait for several weeks before the drug seems to take effect. "There have to be secondary changes that are occurring, which are related to the long-term application of these drugs," he says.
Nairn says the research adds to the understanding of what happens when neurotransmitters are released from one brain cell and then attach to a nearby cell.
"The basic, underlying premise is that if you can understand exactly how those processes occur, then it will give you some better information about how to design new drugs or identify new targets for drugs that will complement or replace existing drugs," Nairn says.
According to Svenningsson, future research could reveal whether drugs designed to target DARPP-32 would be better antidepressants.
What To Do
The Society for Neuroscience publishes this report on serotonin and judgment, or you can check out this reprint from FindArticles.com on SSRIs.
Find out about depression from the National Institute of Mental Health.
