Interaction between perineuronal nets and ketamine in antidepressant action

Depression is the leading cause of disability worldwide, yet its biological mechanisms remain poorly understood. This study investigated whether scaffolding proteins in the medial frontal cortex contribute to antidepressant effects. The researchers injected chABC into the infralimbic cortex of animals to remove perineuronal nets and then tested for antidepressant effects using the forced swim test. They also tested whether systemic ketamine injections added to the effect. Preliminary data indicate that neither removing the scaffolding proteins nor ketamine alone decreased depression-like behavior, but the two treatments may interact synergistically to decrease immobility time in the forced swim test.

Study at a glance

Abstract

Depression is highly prevalent, increases suicide risk, and is now the leading cause of disability worldwide. Our ability to treat depression is hampered by the lack of understanding of its biological underpinnings and of the mode of action of effective treatments. We hypothesised that the scaffolding proteins in the medial frontal cortex play a major role in effective antidepressant action. We implanted cannulae into the infralimbic cortex to inject chABC and locally remove perineuronal nets and then tested for antidepressant effects with the forced swim test. We further tested if systemic injections of ketamine had an additive effect. Our preliminary data indicate that neither the removal of these scaffolding proteins nor ketamine were sufficient to decrease depression-like behaviour, but may interact synergistically to decrease immobility time in the forced swim test.