Caffeine is the most widely used behaviorally active drug in the world which exerts its activity on central nervous system through
adenosine receptors. Worrying data indicate that excessive
caffeine intake applies to patients suffering from
mental disorders, including depression. The main goal of the present study was to evaluate the influence of
caffeine on animals' behavior in forced swim test (FST) as well as the effect of
caffeine (5 mg/kg) on the activity of six typical
antidepressants, such as
imipramine (15 mg/kg),
desipramine (10 mg/kg),
fluoxetine (5 mg/kg),
paroxetine (0.5 mg/kg),
escitalopram (2 mg/kg), and
reboxetine (2.5 mg/kg). Locomotor activity was estimated to verify and exclude false-positive/negative results. In order to assess the influence of
caffeine on the levels of
antidepressant drugs studied, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. The results showed that
caffeine at a dose of 10, 20, and 50 mg/kg exhibited
antidepressant activity in the FST, and it was not related to changes in locomotor activity in the animals.
Caffeine at a dose of 5 mg/kg potentiated the activity of all
antidepressants, and the observed effects were not due to the increase in locomotor activity in the animals. The interactions between
caffeine and
desipramine,
fluoxetine,
escitalopram, and
reboxetine were exclusively of pharmacodynamic character, because
caffeine did not cause any changes in the concentrations of these drugs neither in blood serum nor in brain tissue. As a result of joint administration of
caffeine and
paroxetine, an increase in the
antidepressant drug concentrations in serum was observed. No such change was noticed in the brain tissue. A decrease in the
antidepressant drug concentrations in brain was observed in the case of
imipramine administered together with
caffeine. Therefore, it can be assumed that the interactions
caffeine-
paroxetine and
caffeine-
imipramine occur at least in part in the pharmacokinetic phase.