The influence of caffeine on the activity of moclobemide, venlafaxine, bupropion and milnacipran in the forced swim test in mice

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.…”

“…The antidepressant drugs were given 60 min and DMPX along with DPCPX were given 30 min before behavioural tests. The highest inactive doses of the tested agents and pretreatment schedules were selected based on the literature data and the results of our previous experiments . Additionally, they were confirmed in the conditions of our lab in the preliminary experiments along with the lowest active doses of the used antidepressants (i.e.…”

“…The procedure was carried out according to the method described in details previously . The total duration of immobility was recorded during the last 4 min of the 6‐min testing period.…”

“…Serum and brain levels of moclobemide, venlafaxine and bupropion were determined by a high‐performance liquid chromatography (HPLC) method. The whole procedure was previously described in details . The assays were reproducible with low intra‐ and interday variation (coefficient of variation <10%).…”

Withdrawal of caffeine after its chronic administration modifies the antidepressant-like activity of atypical antidepressants in mice. Changes in cortical expression of Comt, Slc6a15 and Adora1 genes

“…Administration of ineffective doses of caffeine (which acts as a nonselective A 1 and A 2A receptor antagonist) enhanced the activity of ineffective doses of the following antidepressants: imipramine, desipramine, fluoxetine, paroxetine, escitalopram, reboxetine, venlafaxine, mianserin, milnacipran, bupropion, agomelatine, and moclobemide in the FST (Kale and Addepalli 2014; Poleszak et al 2016; Poleszak et al 2015; Szopa et al 2016). On the other hand, the antidepressant-like effect of creatine and ketamine, fast-acting antidepressant agents targeting the glutamatergic system, but not fluoxetine, was abolished by caffeine, DPCPX (a selective adenosine A 1 receptor antagonist), and ZM241385 (a selective adenosine A 2A receptor antagonist), while the administration of ineffective doses of creatine or ketamine combined with CHA (a selective adenosine A 1 receptor agonist), DPMA (a selective adenosine A 2A receptor agonist), or dipyridamole (an adenosine transporter inhibitor) produced a synergistic antidepressant-like effect in the TST (Cunha et al 2015).…”