Table 2.
Effect of P2X7R inhibition in animal models of depression.
| P2X7R Modulation | Specie | Model | Effect | Mechanism Involved | References |
|---|---|---|---|---|---|
| Genetic deletion | mice | FST, TST | Antidepressant-like | IL-1β release absence. | [82] |
| Genetic deletion | mice | FST | Antidepressant-like effect after 3 sessions of FST, but not 1 | Decreased activation of hippocampus dentate gyrus and basolateral amygdala. | [84] |
| Genetic deletion/pharmacological blockade (BBG) | mice | FST, TST | Antidepressant-like | Increased levels of NA in amygdala; and attenuated stress-induced ACTH and corticosterone responses. | [83] |
| Genetic deletion/pharmacological blockade (BBG) | mice | TST and SPT after LPS challenge | Antidepressant-like | Absence of P2RX7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus. | [19] |
| Pharmacological blockade (iso-PPADS) | mice | FST | Antidepressant-like | Decreased NOS1 activation and NO synthesis in prefrontal cortex. | [85] |
| Pharmacological blockade (PPADS) | mice | FST | Antidepressant-like | 5-HT and NA availability. | [92] |
| Pharmacological blockade (A-804598) | FRL/FSL rats | FST | Antidepressant-like | Activation of BDNF signaling pathway in ventral hippocampus. | [80] |
| Pharmacological blockade (A-804598) | rats | CUS/restraint stress | Antidepressant-like | Inhibition of inflammasome activation in the hippocampus. | [22] |
| Pharmacological blockade (A-804598) | rats | Foot shocks | No effect | Partially attenuated the increase in IL-1β and CD14 mRNA in the paraventricular nucleus induced by stress. | [89] |
| Pharmacological blockade (BBG) | mice | TST and SPT after LPS challenge | Antidepressant-like | Decreased serum levels of TNF-α in serum after LPS treatment. | [93] |
| Pharmacological blockade (combined hippocampal microinjection of BBG and A-438079 | rats | CUS | Antidepressant-like | CUS increased ATP and NLRP3 inflammasomal activation in the hippocampus but the effect of P2RX7 blockade was not investigated. | [52] |
| Pharmacological blockade (BBG) | mice | CUMS | Antidepressant-like | Regulation of HPA axis and decrease microglial activation in cortex, hippocampus and basal nuclei. | [86] |
5-HT: 5-hydroxytryptamine or serotonin; ACTH: adrenocorticotropic hormone; ATP: adenosine tri-phosphate; BBG: brilliant blue G; BDNF: brain-derived neurotrophic factor; CD14: cluster of differentiation 14; CUMS: chronic unpredictable mild stress; CUS: chronic unpredictable stress; FRL: flinders resistant line; FSL: flinders sensitive line; FST: forced swim test; HPA: hypothalamic-pituitary-adrenal; IL-1β: interleukin 1β; LPS: lipopolysaccharide; mRNA: messenger ribonucleic acid; NA: noradrenaline; NLRP3: NLR family pyrin domain containing 3; NO: nitric oxide; nNOS: neuronal nitric oxide synthase; P2X7R: P2X7 receptors; PPADS: pyridoxalphosphate-6-azophenyl-2’,4’-disulfonic acid; SPT: sucrose preference test; TNF-α: tumor necrosis factor-α; TST: tail suspension test.