Adenosine signalling drives antidepressant actions of ketamine and ECT.

ABSTRACT: Ketamine and electroconvulsive therapy (ECT) achieve rapid remission in treatment-resistant depression. However, their mechanisms of action-the understanding of which is essential for refining therapeutic precision-remain unclear^1-3. Here, using mouse models, we identify adenosine signalling as a central pathway that underlies the antidepressant effects of these interventions. Results from genetically encoded adenosine sensor experiments and real-time optical recordings reveal that both therapies induce strong adenosine surges in key mood-regulatory regions, including the medial prefrontal cortex and the hippocampus. Genetic or pharmacological disruption of A₁ and A_2A adenosine receptors abolishes their therapeutic effects, which establishes the essential r

SUBMITTER: Yue C 

PROVIDER: S-EPMC12779573 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature