Carleton University’s Argel Aguilar-Valles and Nahum Sonenberg from McGill University’s Department of Biochemistry and Goodman Cancer Centre have published new research in Nature. The paper, Antidepressant Ketamine Actions Engage Cell-Specific Translation Via elF4E, discovered a mechanism mediating the neuronal and behavioral responses to ketamine when used as a treatment for major depression disorder (MDD).

Effective drug therapy for MDD is a challenge, as more than 30 per cent of patients are resistant to the first line of treatment, selective serotonin reuptake inhibitors (SSRIs). However, recent research shows that ketamine provides rapid and long-lasting antidepressant effects in treatment-resistant patients. Yet, this treatment also has numerous, potentially dangerous side effect and can lead to addiction.

“Our discovery advances the understanding of how ketamine works in the brain,” said Aguilar-Valles, professor in the Department of Neuroscience. “We want to understand these powerful antidepressants and find similar results without having the side effects of ketamine.”

Aguilar-Valles started this research six years ago when he was a postdoctoral fellow in Sonenberg Lab at McGill University. He transferred to Carleton on Jan. 2019 and finalized this research for publication.

“With SSRIs, it takes two to three months for the patient to have stable effects,” said Aguilar-Valles. “With ketamine, however, within hours a single dose has an effect that can last a week.”

The research used mice as models to demonstrate that ketamine’s effects on neuronal activity and behavioural effects involve a group of proteins referred to as 4E-BPs. These proteins are central in controlling the production of other proteins in the brain.

The researchers will now try to determine whether this important mechanism is involved in situations of chronic stress, which is a risk factor for MDD. In addition, it is important to determine whether biological sex differences affect the involvement of these proteins for the mechanism of action of ketamine.

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