Extracellular adenosine in acute stress-induced depressive-like behavior: Where does it come from?

Area of Science:

• Neuroscience
• Biochemistry
• Psychiatry

Background:

• Major depressive disorder (MDD) is a common psychiatric condition with complex neurochemical underpinnings.
• Understanding stress-induced neurochemical changes is vital for developing effective depression treatments.

Purpose of the Study:

• To investigate the source and function of extracellular adenosine in the ventral hippocampal CA1 region during acute stress.
• To explore the role of purinergic signaling in stress-induced depressive-like behaviors.

Main Methods:

• Utilized fiber photometry with GRAB fluorescent sensors (GRAB_ATP1.0, GRAB_Ado1.0) in mice to monitor real-time adenosine and ATP dynamics.
• Employed tail suspension test (TST) and foot shock (FS) as acute stress paradigms.
• Used pharmacological blockade to identify adenosine sources and assessed behavioral outcomes.

Main Results:

• Both TST and FS significantly elevated extracellular adenosine levels in the CA1 region.
• Foot shock (FS) uniquely increased extracellular ATP levels.
• TST-induced adenosine primarily stemmed from ENT1/2 transport, while FS-derived adenosine involved ENT1/2 and CD73 pathways.
• Inhibition of these pathways ameliorated FS-induced depressive phenotypes.
• Exogenous ATP or adenosine administration exacerbated depressive-like behaviors.

Conclusions:

• Distinct sources of extracellular adenosine in the ventral hippocampus contribute to acute stress-induced depressive-like behaviors.
• This study elucidates the role of purinergic signaling in stress responses.
• Findings may guide the development of novel therapeutic strategies for mood disorders.