The anxiogenic action of caffeine (10, 25 and 50 mg/kg, i.p.) was inve
stigated in rats and compared with that of yohimbine (2 mg/kg, i.p.).
The experimental methods used were the open-field, elevated plus-maze,
social interaction and novelty-suppressed feeding latency tests. Caff
eine produced a dose-related profile of behavioural changes, which wer
e qualitatively similar to those induced by yohimbine and which indica
te an anxiogenic activity in rodents. Thus, both the drugs reduced amb
ulation and rears, and increased immobility and defaecation in the ope
n-held test. They decreased the number of entries and time spent on th
e open arms of the elevated-plus maze, reduced social interaction in p
aired rats and increased the feeding latency in an unfamiliar environm
ent in 48-h food-deprived rats. Lorazepam, a well known benzodiazepine
anxiolytic agent, attenuated the anxiogenic effects of caffeine and y
ohimbine. Subchronic administration of caffeine (50 mg/kg, i.p.) for 2
1 days, in different groups of animals, induced a significant degree o
f tolerance in the elevated plus-maze test, which was statistically si
gnificant after 14 and 21 days' treatment. Yohimbine, however, did not
induce similar tolerance. When caffeine (50 mg/kg, i.p.) was withdraw
n after 21 days' administration, to a separate group of rats, signific
ant withdrawal anxiety was observed 48 h later as noted in the elevate
d plus-maze test. The investigations support clinical evidence of caff
eine-induced anxiety, tolerance to anxiety on continued use, and withd
rawal anxiety in chronic caffeine-containing beverage users.