Stimulating dopamine-releasing neurons immediately extinguishes depression in mice
MIT and Stanford University researchers recently pinpointed brain cells that could be new targets for treating depression, which affects an estimated one in 10 Americans.
By stimulating these cells to deliver dopamine to other parts of the brain, the researchers were able to immediately eliminate symptoms of depression in mice. They also induced depression in normal mice by shutting off the dopamine source.
“The first step to achieving a new era of therapy is identifying targets like these,” says Kay Tye, an assistant professor of brain and cognitive sciences at MIT and a member of MIT’s Picower Institute for Learning and Memory. She says she hopes the fact that this target exists “motivates drug companies to revitalize their neuroscience research groups.”
Many depressed patients are prescribed drugs, including Prozac, that boost the brain chemical serotonin. However, these require four to six weeks to take effect, suggesting that serotonin may not be part of the brain system most responsible for depression-related symptoms, Tye says. Finding more specific targets, rather than dousing the whole brain in chemicals, is the key to developing better therapies, she believes.
In the new study, published in Nature, the researchers genetically engineered neurons to produce a light-sensitive protein that regulates the flow of ions in and out of the cell; exposing the neurons to light turns them on or off nearly instantaneously. This approach, known as optogenetics, allowed the team to selectively inhibit or stimulate dopamine-releasing neurons in the ventral tegmental area (VTA).
The VTA is a primary source of dopamine in the brain. When the research team turned off dopamine-releasing neurons in the VTA of normal mice, it immediately provoked depression-like symptoms, including a decline in motivation to explore a new setting and the inability to feel pleasure (measured by how much the mice preferred sugar water over plain water).
Next, the researchers tested what would happen if they turned on VTA neurons in mice showing symptoms of depression induced by mild stress such as disruptions in circadian rhythms, social isolation, overcrowding, or changes in temperature. Bursts of activity in the neurons flooded their brains with dopamine and restored normal behavior patterns within about 10 seconds.
Neurons in the VTA send dopamine to many different parts of the brain, but the researchers found that dopamine signals sent to the nucleus accumbens, known to play a role in motivation, pleasure, fear, and addiction, appear to have the most important role in controlling depression.
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