Work

Adenosine as the metabolic common path of rapid antidepressant action: The coffee paradox

Year: 2025

Type: article

Abstract: Yue, Luo, and colleagues discovered that adenosine signalling is the common underlying mechanism of rapid acting antidepressant therapies, unifying the effects of ketamine, ECT and acute intermittent hypoxia. They use genetically encoded sensors, along with extensive mechanistic dissection, to show that all three induce adenosine surges in mood-regulatory circuits via A1 and A2A receptor activation. The mechanism of action of ketamine primarily involves modulation of mitochondrial metabolism as opposed to NMDA receptor antagonism, thereby presenting the possibility for improvements in derivative products with better therapeutic indices. These outcomes offer a rational framework for gauging therapeutic benefit for depression and raise vexing questions about patterns of caffeine consumption in treatment resistant depression, specifically whether the chronic use has a protective effect or whether the acute use impedes treatment response.

Source: Brain medicine :

DOI: 10.61373/bm025c.0134

Authors: Julio Licinio, Ma-Li Wong

Language: English

Topic: Treatment of Major Depression

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funder: National Institute of Mental Health

Awards: Mechanisms of noncanonical caspase 1 signaling in the brain., G1488684004, Dissecting the roles of an epigenetic regulator of genes involved in synaptic plasticity and social cognition.