Dose-dependent effects of caffeine on behavior and thermoregulation in a chronic unpredictable stress model of depression in rats.

The effects of the non-selective adenosine A(1)/A(2) receptor antagonist caffeine on behavior and thermoregulation in chronic unpredictable stress (CUS) model of depression was studied in Wistar rats. In the open field (OF) test, caffeine dose-dependently increased motor activity while decreased grooming and time spent in the corner. Five-week exposure to CUS procedure had the opposite effect in rats. Caffeine reversed CUS-induced effects on the above mentioned parameters. Caffeine (40 mg/kg) increased the motor activity in plus maze (PM) test while at doses of 20 and 40 mg/kg it decreased the number of entries in the open arms. Whereas CUS did not change the level of anxiety, caffeine (2, 20 and 40 mg/kg) administered after CUS diminished it by increasing the time in open arms. Caffeine dose-dependently decreased the immobility time while CUS had the opposite increasing effect in forced swimming test (FST). Caffeine at doses of 20 and 40 mg/kg reversed the effect of CUS on immobility in FST. Caffeine produced dose-dependent rice of body temperature in both non-treated and CUS-treated rats. The hyperthermic effect in normal rats pretreated with caffeine lasted about 90 min while in caffeine-pretreated rats exposed to CUS it lasted about 150 min. High dose of caffeine (100mg/kg) induced significant hypothermia between 90th and 150th minute in control rats and hyperthermia between 30th and 60th minute in CUS-treated rats. These results suggest a putative role of this methylxanthine in the adaptive responses to chronic unpredictable stress stimuli.