The striatum, a large cluster of nerve cells tucked away within the depths
of each hemisphere of the brain and heavily dependent on the neurotransmitter
dopamine, is crucial for motion control, reward, and emotion. And new research
suggests that the SSRI antidepressants may have some part to play with this
Studies have suggested that depression might involve the striatum. For
example, the concentration of dopamine and the density of striatal dopamine
transporters were found to be abnormal in patients with major depressive
disorder. Previous research has suggested that the actions of antidepressants
are influenced by dopamine and by the interplay of serotonin and dopamine.
John Dani, Ph.D., a professor of neuroscience at Baylor College of
Medicine, and colleagues treated striatal slices from mouse brains with the
SSRI antidepressant fluoxetine. They found that such treatment tricked
transporters on striatal nerves that use dopamine as their neurotransmitter
into ferrying serotonin instead of dopamine into striatal nerve terminals.
Further, serotonin carried into these terminals was subsequently discharged
along with dopamine. When the researchers injected mice with fluoxetine, it
seemed to lead to the same serotonin "freeloader" phenomena in the
striatum that fluoxetine treatment had produced in vitro. The researchers
reported their findings in the April 7 Neuron.
In an accompanying editorial, David Sulzer, Ph.D., an associate professor
of psychiatry at Columbia University, and Robert Edwards, M.D., a professor of
neurology at the University of California, San Francisco, said, "The
evidence that antidepressants induce serotonin accumulation by dopamine
neurons has now been significantly advanced.... [However,] it is not yet known
if such serotonin release by dopamine neurons contributes to the therapeutic
effect of these agents."
Dani and his coworkers think that it might. "We can conclude...that
the extremely dense dopamine transporters in the striatum are able to
transport serotonin into dopamine terminals when extracellular serotonin is
elevated," they said in their report. "Normally, this process may
be of little significance because of its low efficiency and the low
extracellular serotonin concentration. However, it may play a functional role
when serotonin is elevated for prolonged times during treatment with SSRI-type
The study was funded by the National Alliance for Research on Schizophrenia
and Depression and the National Institutes of Health.
An abstract of "Corelease of Dopamine and Serotonin From
Striatal Dopamine Terminals" is posted online at<www.neuron.org/content/article/abstract?uid=PIIS0896627305001261>.▪