In another study, Bhattacharya et al. reported that subchronic injection of caffeine (50 mg/kg) for 21 days, in different groups of animals, induced anxiety-like behavior.[2] The researchers observed that rats who received caffeine injections had decreased number of entries and time spent on the open arms of the elevated plus maze, reduced social interaction with other rats, and increased feeding latency in an unfamiliar environment – all of these behaviors are indicative that caffeine has an anxiogenic effect.

Caffeine and Recognition Memory

The benefits of caffeine on cognition in rodents is well characterized. In one study, Costa et al. found that caffeine consumed in adulthood may prevent recognition memory decline with aging.[3] The researchers evaluated adulthood administration of caffeine up to old age on recognition memory in mice using the object recognition test (ORT). This test involves the presentation of two similar objects in mice during the first session, and then one of the two objects is replaced by a new one during the second session. If recognition memory is functioning normally, the mouse will spend more time exploring the new object than the familiar object. However, if exploration of all objects is the same, the mouse is considered to have memory deficit. The researchers fed adult mice (6 months old) with either drinking water or caffeine (1 mg/mL) for 12 months. At 18 months of age, the researchers tested both groups using object recognition test and found that aged mice displayed lower performance in the recognition memory compared with adults (6 months old). In addition, the mice which were treated with caffeine showed similar performance to adult mice during the object recognition test and displayed improvement compared with the age-matched control mice.

In another study, Onaolapo et al. found that caffeine administration improves recognition memory in mice.[4] The researchers performed Y-maze test and object recognition test. Mice were injected with a single dose of caffeine 30 minutes before Y-maze exploration. For the object recognition test, the researchers administered caffeine 30 minutes before training and another dose 30 minutes before commencing the test. Results of object recognition test showed that female mice spent more time exploring the new object than the familiar object compared to male mice, suggesting that caffeine injection improved non-spatial memory retention in female mice but not in males. On the other hand, the results of the Y-maze test showed that male mice were able to perform successive entries into the three arms of the maze compared to female mice, indicating that spatial working-memory is improved in males but not in females. These results suggest that caffeine can improve recognition memory in a sex-dependent manner.