Understanding the unhappy side of serotonin

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ANTIDEPRESSANTS such as Prozac and Zoloft offer relief for over 100 million people around the world who have depression, but with a potentially serious side effect. In the first few weeks, feelings of fear and anxiety can get worse.
Antidepressants can help improve mood, but not always immediately.
Now, scientists believe they have identified what happens in the brain to cause this, according to research published in Nature.
Selective serotonin reuptake inhibitors (SSRIs) are used to treat anxiety, depression, and related conditions. Around 10 percent of people in the United States use them, including 1 in 4 women in their 40s and 50s.
Serotonin, a neurotransmitter, is the “happy hormone” thought to boost feelings of well-being. Abnormally low levels of serotonin have been linked to depression. SSRIs are thought to improve mood by boosting serotonin activity in the brain.
But serotonin is not always a bed of roses. In the early days of treatment, it can increase levels of fear and anxiety and even suicidal thinking in some younger people. As a result, patients may stop using the treatment after a few weeks.
When serotonin works through certain brain circuits, it seems to improve mood, but when but it acts on others circuits, the effect is different.
Mapping the serotonin-driven anxiety circuits
Researchers from the University of North Carolina Medical School in Chapel Hill, NC, have identified a circuit that seems to be related to serotonin-driven anxiety.
1 percent of Americans aged over 12 years use antidepressants Over 60 percent have used them for more than 2 years Women are more likely to use antidepressants than men.
Learn more about antidepressants Using a range of methods, such as advanced optogenetic and chemogenetic tools, the team was able to trace a serotonin-activated pathway in the brains of mice that appears to drive anxious behavior.
First, the team delivered a mild shock to the paws of mice – a standard way of triggering behaviors related to fear and anxiety. This was shown to activate serotonin-producing neurons in the dorsal raphe nucleus (DRN).
The DRN is a brainstem region associated with mood and depression. DRN serotonin neurons project to a brain region known as the bed nucleus of the stria terminalis (BNST). Previous studies have shown that BNST is involved when serotonin triggers a negative mood in rodents.
When the team artificially increased the activity of the DRN-to-BNST neurons in the mice, anxiety-like behaviors increased.