Mapping ketamine-orchestrated translatome to rapid-acting anti-anhedonic effects at the synaptic level with cell-type specific resolution

2021 Pilot Project Read More


Principal Investigator: Marco Pignatelli (WashU Psychiatry)
Collaborator: Vijay Samineni (WashU Anesthesiology)


Anhedonia—defined as diminished pleasure from, or interest in, previously rewarding activities—is a widely reported symptom of many psychiatric and neurological illnesses. A promising and novel treatment for anhedonia is represented by ketamine. Indeed, recent clinical evidence has shown that a single injection of ketamine ameliorates anhedonic symptoms within a matter of hours. However, understanding of the neurobiological mechanisms underpinning ketamine’s anti-anhedonic effects is lacking. Accordingly, the goal of this proposal is to develop a circuit and synaptic framework for ketamine’s mechanism of action in alleviating anhedonia. Specifically, using chronic stressed mice as a model system, we are planning to identify specific cellular and synaptic elements recruited by in vivo K administration and responsible for its anti-anhedonic effects within the Nucleus Accumbens, a brain region critical for mood and hedonic drive. No therapeutics are currently approved for the treatment of anhedonia despite its prevalence across multiple psychiatric and neurological disorders, therefore identifying mechanisms mediating ketamine’s ability to ameliorate hedonic deficits may provide cardinal stepping stones toward treatment improvements for this tractable endophenotype.


Pilot project teams include Hope Center faculty members and others. For more about Hope Center faculty on this team, click below.

Marco Pignatelli