Mechanisms of the sustained antidepressant effects of ketamine

This project led by Joe Flanagan in collaboration with Emma Robinson’s group and Boehringer Ingelheim aims to better understand the sustained antidepressant effects of the NMDA receptor antagonist ketamine.

Aim:

Ketamine has shown promise as a potential therapeutic due to its sustained antidepressant effects. How ketamine, an antagonist to NMDA receptors, results in these effects is unclear.

We aim to investigate synaptic and circuit alterations within the medial prefrontal cortex in response to ketamine administration to help us better understand its sustained antidepressant effects.

Hopefully inspiring future drug discovery into ketamine analogues with similar antidepressant effects and a reduced side effect burden.

Techniques:

To achieve these goals, we are performing ex vivo brain slice electrophysiology in the mPFC to measure synaptic plasticity mechanisms whilst characterising, at the subcellular level, the changes in transcriptomics with single-cell RNA sequencing.