Nav: Home

Novel mode of antidepressant action may help patients unresponsive to SSRIs

April 25, 2017

Osaka - Antidepressants treat symptoms of depression by increasing levels of brain signaling molecules (neurotransmitters) such as serotonin, as with the most widely used type of antidepressant, selective serotonin reuptake inhibitors (SSRIs). However, many of the 350 million people worldwide thought to be affected with depression do not respond to SSRI treatment.

Now, researchers in the Department of Neuroscience and Cell Biology at Osaka University have found that an activator of the serotonin type 3 receptor (5HT3R) produces antidepressant effects in mice and increases nerve cell growth in the part of the brain responsible for memory and spatial navigation (the hippocampus). They also showed that it functions using a different mechanism than the commonly used SSRI fluoxetine, and therefore may be suitable for patients with depression who do not respond favorably to current medication.

The team of researchers used mice lacking part of 5HT3R to explore the function of the 5HT3R activator. The activator had antidepressant effects and initiated nerve cell growth in the hippocampus in control mice but not in those lacking part of the receptor.

In contrast, fluoxetine showed similar antidepressant actions and nerve cell growth in both control and knockout mice because it requires the type 1A rather than 5HT3R for its actions.

To explore the 5HT3R activator mode of action, hippocampal nerve cells expressing the receptor were chemically stained to investigate protein expression. The same cells were shown to express both the receptor and the growth factor IGF1.

"Treatment of control mice with the receptor activator led to increases in IGF1 secretion," study coauthor Shoichi Shimada says. "However, the activator had no effect in mice lacking part of the receptor." In addition, protein signaling involving IGF1 in the hippocampus was found to be necessary for nerve cell growth that was dependent on 5HT3R.

Fluoxetine must be given to patients for long periods to have any antidepressant effect, but just 3 days of 5HT3R activator treatment produced notable responses in mice.

"IGF1 combined with the activator produced characteristic changes in nerve cell growth that were not seen following fluoxetine administration," corresponding author Makoto Kondo says. "This may explain why the response times are so different."

Another difference is that the type 1A and 5HT3R are expressed in different cell types of the hippocampus which adds support to their use of distinct mechanisms of antidepressant action.
-end-


Osaka University

Related Depression Articles:

Tackling depression by changing the way you think
A thought is a thought. It does not reflect reality.
How depression can muddle thinking
Depression is associated with sadness, fatigue and a lack of motivation.
Neuroimaging categorizes 4 depression subtypes
Patients with depression can be categorized into four unique subtypes defined by distinct patterns of abnormal connectivity in the brain, according to new research from Weill Cornell Medicine.
Studies suggest inflammatory cytokines are associated with depression and psychosis, and that anti-cytokine treatment can reduce depression symptoms
Studies presented at this year's International Early Psychosis Association meeting in Milan, Italy, (Oct.
Is depression in parents, grandparents linked to grandchildren's depression?
Having both parents and grandparents with major depressive disorder was associated with higher risk of MDD for grandchildren, which could help identify those who may benefit from early intervention, according to a study published online by JAMA Psychiatry.
More Depression News and Depression Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...