Fig. 3: Effects of caffeine in animal models of anxiety.

Different acute and chronic protocol stress induction was selected. Different behavior tests evaluated anxiety, depression, and cognitive functions. In acute stress, there was an increase in pro-inflammatory (interleukin 6 - IL-6; interleukin ß1 - IL1-ß, and TNF-alpha) and a decrease in anti-inflammatory (interleukin 4 - IL-4; interleukin 10 - IL10) cytokines and BDNF. At the cellular level, activation of astrocytes and microglia, neuronal damage, and neutrophil infiltration in the brain were also demonstrated. Oxidative stress was observed with increased lipid peroxidation, as measured by malondialdehyde (MDA), nitric oxide (NO), superoxide radical formation, and a decrease in glutathione (GSH) content. In chronic stress, there was an increase in pro-inflammatory cytokines (IL-6; TNF-alpha, IL1-ß) in glucose levels and acetylcholinesterase (AChE). The level of oxidative stress markers was decreased (catalase, Glutathione S-Transferase – GST, Glutathione Peroxidase – GPx, TAC - Total Antioxidant Capacity) as well as the level of serotonin (5-HT), dopamine, and norepinephrine (NORE). Neuronal damage was also observed. In all articles selected for this review, caffeine treatment, directly or indirectly, reversed the behavioral, cellular, and molecular changes described in the models. Created in BioRender. Campello-Costa, P. (2025) https://BioRender.com/o80f263.