Table 1 Main effects of caffeine administration on neuroinflammatory and behavioral outcomes in animal models of anxiety.
Author, Year | Anxiety Model | Animal | Caffeine Exposure | Other Substances | Behavior Test | Inflammatory markers | Other effects | |
|---|---|---|---|---|---|---|---|---|
Lind et al. [26] | Animals selected in the EPM: Control, LOAT - high anxiety, HOAT – Low anxiety | Adult Male Wistar rats | Caffeine (50 mg.kg-1) Subcutaneous Acute (2 doses in 2 days) | No | Caffeine: Anxiogenic for high anxiety group in the MCSF. | nd | Caffeine: Increases corticosterone in the anxiety groups; | |
Wadhwa et al. [27] | Sleep deprived for 48 | Adult Male Sprague–Dawley rats | Caffeine (60 mg.kg-1) Gavage. Acute (48 h) | Modafinil (100 mg.kg-1/day) for 48 h | Caffeine: Anxiolytic in the EPM and OFT. | Caffeine: Anti-inflammatory (reduces IL-6, TNFα, IL-1ß, and increase IL-10 and IL-4) in the brain and plasma; decrease microglial reactivity; | No other effect | |
Çakır et al. [28] | Acute stress - cat odor stress Chronic stress (restraint overcrowding, cat odor, elevated plus maze, and forced swim | Adult Male Sprague–Dawley rats | Caffeine Acute (1 day) or Chronic (2 weeks) (3 mg.kg-1 ip.) | No | Caffeine: Anxiolytic in both acute and chronic stress in the HBT; Antidepressant for chronic stress. | Caffeine: Anti-inflammatory (decreases MPO activity, neutrophil infiltration in the brain) | Chronic caffeine: Improves memory in the ORT after chronic and acute stress; and decrease MDA, NO, and lucigenin levels after acute stress; MDA and NO levels declined by acute caffeine; Acute caffeine decreased SOD activity and improved glutathione and luminol levels. | |
Dias et al. [29] | repeated physical restraint (4 h/day for 2 weeks) | Adult Male Wistar rats | Caffeine (0.3 g.L-1) Orally (3 weeks) | P2X7R- antagonist (BBG, 45 mg.kg-1, i.p) | Caffeine: Anxiolytic in the OFT, EPM, antidepressant in the SPT, FST, and improve memory in the Y maze, ODT. | Caffeine: Anti-inflammatory (reduces TNFα, IL-1ß; decrease in Iba-1 marker) | Caffeine: Down-regulates P2X7R and A2a adenosine receptor. | |
Okeowo et al. [42] | Chronic Unpredictable Mild Stress (CUMS) | Adult Male Wistar rats | Caffeine (12.5, 25, 50 mg.kg1) Gavage Chronic (2 weeks) | No | Caffeine: Anxiolytic in EPM and DLB, antidepressant in SPT and FST, and protects against UCMS-induced memory impairment in Y maze and ORT. | Caffeine: Reverts changes in GFAP and iba-1 decrease induced by CUMS). | Caffeine: Decreases glucose (blood) and corticosterone (Serum), decreases AchE level, increases NORE, Dopamine, and Serotonin, Decrease TAC, GPx, CAT, and GST activities; Antioxidant effect (Reverts changes in oxidative stress | |
Sabry et al. [30] | Caffeine + Sodium benzoate during adolescence | Adolescent Male Albino rats | Caffeine (30 mg.kg-1 ip.) Chronic (4 weeks) | Sodium benzoate 100 and 400 mg.kg-1p.o. | Caffeine: Anxiolytic effect in the DLB and SAT, increase exploratory activity. | Caffeine: Increases MDA and NO in cortex and MPO activity in the hippocampus (neutrophil infiltration in the brain) Caffeine + Sodium benzoate: Decreases GSH (cortex) | Caffeine: Increases Dopamine (cortex, hippocampus), increases (cortex) and decreases (hippocampus) GABA; Caffeine + Sodium benzoateincrease - AChE content in the frontal cortex; Some pyknotic nuclei in cortex and hippocampus; | |
Chen et al. [41] | Chronic Unpredictable Mild Stress (CUMS) | Adult Male Sprague–Dawley rats | Chaigui Granules (CG – six herbal medicines) and Xiaoyao San (XYS - consists of six Chinese herbs Gavage (4 weeks) | No | Chaigui Granules: Antidepressant SPT, FST, OFT and EPM. | Chaigui Granules: Anti-inflammatory inhibits the xanthine- P2X7R-NLRP3 inflammasome pathway, decrease TNFα, IL-1ß; IL-6, MDA, increase SOD | Chaigui Granules: Neuroprotection (reduction of xanthine content and decrease ROS) | |
Mingori et al. [31] | Caffeine and guarana extract (CGE) | Middle Age Male Wistar rats | Caffeine 0.84 mg.kg-1 gavage Chronic (6 months) | CGE - 21 mg.kg1 | Caffeine: Anxiolytic effect in the OFT. | Nd. | Caffeine: neuroprotection (decrease pAKT – hippocampus and striatal p38); Modulates catalase and GST tissue-specific. Caffeine and guarana extract: Increases RAGE; Improve memory in ORT (but not Caffeine and guarana extract). | |
