BACKGROUND AND AIMS: Though depression is known as one of the most frequent chronic health problems in the world, the optimal treatment of the depressed patients remains an important challenge. Due to serious adverse reactions and common ineffectiveness, the conventional antidepressant therapy is usually not sufficient. The identification of the best treatment strategies and development of new, safer, and more effective ones are crucial. Literature data confirm participation of adenosine neurotransmission in the development of depression. Adenosine, which is responsible for the suppressed release of serotonin, noradrenalin, and dopamine, contributes to a decrease of neuronal excitability. The main objective of our study was to investigate an antidepressant activity of a joint administration of adenosine A2A receptor antagonist DMPX (3,7-dimethyl-1-propargylxanthine) and the common antidepressant drugs: imipramine, reboxetine, escitalopram, tianeptine, venlafaxine, moclobemide, and agomelatine. METHODS: The experiments were carried out on male Albino Swiss mice. The antidepressant-like effect was assessed by the forced swim test. In order to avoid the risk of obtaining the false positive/negative effects, the spontaneous locomotor activity was measured as well. RESULTS: The obtained results demonstrated that DMPX at the dose of 3 mg/kg significantly enhanced the antidepressant-like effect of imipramine (15 mg/kg), reboxetine (2.5 mg/kg), escitalpram (2 mg/kg), tianeptine (15 mg/kg), venlafaxine (1 mg/kg), moclobemide (1.5 mg/kg), and agomelatine (20 mg/kg). None of the used combinations changed the overall spontaneous locomotor activity of the animals. CONCLUSION: Forced swim test outcomes indicated a synergistic action of adenosine A2A receptor antagonist in combination with the tested antidepressants.
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