Caffeine enhances the antidepressant-like activity of common antidepressant drugs in the forced swim test in mice

Abstract

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.

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Low dose of caffeine enhances the efficacy of antidepressants in major depressive disorder and the underlying neural substrates

“…Caffeine is one of the most frequently used psychoactive substances ingested mainly via beverage products and some foods by millions of people around the world. Recently, it was evidenced that caffeine enhanced the antidepressant‐like activity of six typical antidepressants including imipramine, desipramine, fluoxetine, paroxetine, escitalopram, and reboxetine in the forced swim test in mice . Moreover, the anxiogenic and helpless‐like behavior and decreased memory performance induced by chronic unpredictable stress were prevented by caffeine administration .…”

The influence of selective A1 and A2A receptor antagonists on the antidepressant-like activity of moclobemide, venlafaxine and bupropion in mice

“…In our previous in‐vivo studies, we showed that caffeine, a non‐selective inhibitor of the adenosine receptors, not only exerted by itself an antidepressant‐like activity in the FST and the TST in mice when given acutely, but also potentiated the effect of antidepressant drugs belonging to different pharmacological groups . It is generally known that caffeine antagonizes all four adenosine receptor subtypes and also acts as a phosphodiesterase inhibitor; therefore, the observed results could have been a resultant of this multiway antidepressant mechanism of action.…”