Modulation of the hypothalamo-pituitary-adrenocortical axis by caffeine

Although caffeine is the most consumed psychoactive substance in the world, the extents of many of its effects are unknown. High doses of caffeine have been shown to activate the HPA axis while the effects of low to moderate doses have usually not been described in detail. Moreover, although several lines of evidence suggest that low doses of caffeine may restrain some negative affective states, the possible modulatory role of caffeine on HPA axis activation induced by a stressful stimulus has not been described. Thus, the present studies investigated the possible modulatory effects of low to moderate doses of caffeine on moderate to high HPA axis activation induced by different intensities of loud noise. First, in order to test this modulation, time courses for adrenocorticotropic hormone (ACTH) and corticosterone responses to loud noise stress and to caffeine were defined, in rats. Plasma ACTH and corticosterone levels peaked 30 min from the onset of noise presentation, and rapidly declined after noise termination. A low caffeine dose of 2 mg/kg significantly increased plasma corticosterone and ACTH levels 30 min following injections, but levels returned to baseline 60 min following injections. Caffeine doses of 30 mg/kg and higher elevated plasma hormone levels for at least 2h. Doses of 2 or 10mg/kg, however, did not modulate endocrine responses to loud noise presentation. It is concluded that although caffeine activates the HPA axis, low to moderate doses do not modulate HPA axis responses to stressful stimuli.