Protective effect of low dose caffeine on psychological stress and cognitive function

Physiol Behav. 2017 Jan 1:168:1-10. doi: 10.1016/j.physbeh.2016.10.010. Epub 2016 Oct 13.


Introduction: Caffeine is an adrenergic antagonist that enhances neuronal activity. Psychological stress depresses cognitive function.

Aim: To investigate the effects of acute and chronic low dose caffeine on anxiety-like behavior and cognitive functions of acute or chronic psychological stressed rats.

Material-method: Acute or chronic caffeine (3mg/kg) was administered to male Sprague Dawley rats (200-250g, n=42) before acute (cat odor) and chronic variable psychological stress (restraint overcrowding stress, elevated plus maze, cat odor, forced swimming) induction. Anxiety and cognitive functions were evaluated by hole-board and object recognition tests. The brain glutathione and malondialdehyde assays, myeloperoxidase, nitric oxide (NO), superoxide dismutase (SOD), luminol and lucigenin activity and histological examination were done. ANOVA and Student's t-test were used for statistical analysis.

Results: The depressed cognitive function with chronic stress exposure and the increased anxiety-like behavior with both stress inductions were improved via both caffeine applications (p<0.05-0.001). Both caffeine pretreatments in chronic stressed rats, and chronic caffeine in acute stressed ones reduced the elevated myeloperoxidase activities (p<0.05-0.01). The increased malondialdehyde, lucigenin and NO levels with acute stress were inhibited with chronic caffeine (p<0.05-0.01), malondialdehyde and NO levels were declined by acute caffeine (p<0.001). Acute caffeine decreased SOD activity (p<0.01) and improved glutathione (p<0.01) and luminol levels (p<0.05). The induced histological damage with both stress exposures was ameliorated with chronic caffeine.

Conclusion: The increased anxiety-like behavior and depleted cognitive functions under stress conditions were improved with both acute and predominantly chronic caffeine pretreatments by decreasing oxidative damage parameters.

Keywords: Acute stress; Anxiety; Chronic stress; Oxidative damage; Working memory.

MeSH terms

  • Animals
  • Caffeine / therapeutic use*
  • Cats
  • Central Nervous System Stimulants / therapeutic use*
  • Cognition Disorders / etiology
  • Cognition Disorders / prevention & control*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Exploratory Behavior / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Maze Learning
  • Nitric Oxide / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Restraint, Physical / adverse effects
  • Stress, Psychological / complications*
  • Stress, Psychological / etiology
  • Stress, Psychological / prevention & control*
  • Swimming / psychology
  • Time Factors


  • Central Nervous System Stimulants
  • Reactive Oxygen Species
  • Nitric Oxide
  • Caffeine