Purinergic transmission in depressive disorders

• Published in: Pharmacology & therapeutics (Oxford) Vol. 224; p. 107821
• Main Authors: Szopa, Aleksandra, Socała, Katarzyna, Serefko, Anna, Doboszewska, Urszula, Wróbel, Andrzej, Poleszak, Ewa, Wlaź, Piotr
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.08.2021
• Subjects: Adenosine receptors; Depression; Depressive Disorder - metabolism; Humans; Locomotor activity; P2X receptor; P2Y receptor; Purinergic transmission; Receptors, Purinergic - metabolism; Signal Transduction; DPMA; PR; CPT; ADP; E–NPPs; NBTI; UTP; E–NPTDases; UCMS; P2Y receptor; SPT; ADPβS; αβ–MeATP; DPCPX; PPADS; Locomotor activity; UDP; Adenosine receptors; AMP; FST; s.c; i.p; P2X receptor; Purinergic transmission; mGlu5; TST; EHNA; GPCR; SAH; NO; TNF–α; CNS; ENT; cAMP; CCPA; LPS; CSC; CSF; NLRP3; R–PIA; BzATP; ARs; BDNF; Depression; S–PIA; p.o; DMPX; NECA; PD; i.c.v; LH; ATP; CHA
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2021.107821

Purinergic signaling involves the actions of purine nucleotides and nucleosides (such as adenosine) at P1 (adenosine), P2X, and P2Y receptors. Here, we present recent data contributing to a comprehensive overview of the association between purinergic signaling and depression. We start with background information on adenosine production and metabolism, followed by a detailed characterization of P1 and P2 receptors, with an emphasis on their expression and function in the brain as well as on their ligands. We provide data suggestive of altered metabolism of adenosine in depressed patients, which might be regarded as a disease biomarker. We then turn to considerable amount of preclinical/behavioral data obtained with the aid of the forced swim test, tail suspension test, learned helplessness model, or unpredictable chronic mild stress model and genetic activation/inactivation of P1 or P2 receptors as well as nonselective or selective ligands of P1 or P2 receptors. We also aimed to discuss the reason underlying discrepancies observed in such studies.