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Treatment-resistant depression: mouse study reveals surprising new insights


January 29, 2024

Dr. Paul Albert“Our results suggest that serotonin and norepinephrine systems are connected, so that drugs that target several neurotransmitters may be more effective for treatment-resistant depression than targeting serotonin alone.” – Dr. Paul AlbertDr. Paul Albert’s team found that not one, but two systems of neurotransmitters play a key role in mouse models of treatment-resistant depression. 

SSRIs (selective serotonin reuptake inhibitors) are the frontline treatment for major depression. Unfortunately, SSRIs do not work for 70% of patients, and the best treatment approach for this population is unclear. 

To explore other options for these patients, Dr. Albert’s team created mouse models of treatment-resistant depression using a genetic mutation that reduces levels of serotonin, which controls feelings of well-being and happiness. 

In a study published in the Journal of Neuroscience, they found surprisingly that these mice also had reduced network activity of norepinephrine, another neurotransmitter involved in depression. When these mice were treated with desipramine, an antidepressant that targets both serotonin and norepinephrine, their depression-like behaviours improved, and their norepinephrine network activity improved.

“Our results suggest that serotonin and norepinephrine systems are connected, so that drugs that target several neurotransmitters may be more effective for treatment-resistant depression than targeting serotonin alone.” – Dr. Paul Albert, senior scientist at The Ottawa Hospital, professor in the University of Ottawa Brain and Mind Research Institute.

Authors: Faranak Vahid-Ansari, Amin Zahrai, Mireille Daigle, Paul R. Albert

Funding: This study was supported by the Canadian Institutes of Health Research and University of Ottawa Brain and Mind Research Institute. All research at The Ottawa Hospital is enabled by generous donors to The Ottawa Hospital Foundation.

Core Resources: Cell Biology and Image Acquisition Core, University of Ottawa Behavioral Core

The Ottawa Hospital is a leading academic health, research and learning hospital proudly affiliated with the University of Ottawa.

 

Scientific Program tags: Neuroscience Program