Dopamine May Play New Role in Depression
High Level of the Feel-Good Brain Chemical May Cause Depression
July 28, 2005 -- A chemical in the brain normally associated with feelings
of happiness and pleasure may also raise the risk of depression.
Researchers say they've found a new way in which prolonged exposure to the
chemical messenger dopamine may play a role in depression as well as drug
addiction. If confirmed by further studies, they say the discovery could lead
to a new understanding of these complex disorders as well as better
Current antidepression treatments are mostly based on the deficiency or
imbalance of the brain chemicals serotonin and norepinephrine, says researcher
Li-Huei Tsai, a professor of pathology at Harvard Medical School, in a news
"This new study highlights the importance of the dopamine system, a less
appreciated target in the current antidepression therapies," he says.
Short-term surges of dopamine are normally associated with feelings of
pleasure. But abnormally high concentrations of the chemical messenger are
linked to schizophrenia, attention deficit disorder, and other psychiatric
Two new studies looking at the association of dopamine, depression, and
other psychiatric conditions appear in the current issue of Cell.
Dopamine and Depression
The studies show that certain receptors in the brain respond to dopamine in
a previously unknown way that occurs over a period of hours rather than minutes
or seconds. In this manner, researchers say the chemical may affect the brain
Receptors are proteins found on the surface of nerve cells that recognize
and translate the signals from a chemical messenger to trigger a response by
In laboratory tests with mice, researchers found prolonged exposure to
dopamine through this pathway inactivated a regulatory protein in the brain
known as Akt and caused the mice to behave like they were depressed in response
In addition, inactivation of this protein caused a molecular chain of events
that caused the mice to become desensitized to certain drugs.
Researchers say this type of prolonged exposure to dopamine may also help
explain the impact of drug abuse on the brain. Most addictive drugs, such as
cocaine and amphetamines, directly or indirectly raise dopamine levels, and the
chemical plays a major role in drug-induced highs.
"This mechanism appears to be more important than those earlier
described for prolonged stimulation by dopamine, as would be the case in those
with psychiatric conditions," says researcher Marc Caron, PhD, professor of
cell biology at Duke University, in a news release.
"The new pathway can now be evaluated for potential new inhibitors that
might be better at controlling particular psychotic behaviors."