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

OBJECTIVE

The main goal of our study was to investigate whether a selective antagonism of the adenosine A or A receptors is able to enhance the antidepressant activity of commonly prescribed drugs.

MATERIALS AND METHODS

All experiments were carried out on male Albino Swiss mice. The forced swim test and the tail suspension test were used to evaluate the antidepressant-like potential. Drug concentrations in animals' serum and brains were measured by high-performance liquid chromatography.

KEY FINDINGS

The antidepressant potential of moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg) and bupropion (10 mg/kg) was enhanced by a co-administration with 3,7-dimethyl-1-propargylxanthine (DMPX; an antagonist of adenosine A receptors; 3 mg/kg) or 8-cyclopentyl-1,3-dipropylxanthine (an antagonist of adenosine A receptors; 1 mg/kg). However, significant interactions between the tested substances were detected only in the experiments with DMPX. The nature of the observed interplays is rather pharmacodynamic than pharmacokinetic, because neither serum nor brain concentrations of the used drugs were significantly increased.

CONCLUSIONS

Blockage of the adenosine receptors (particularly the A subtypes) could be considered in future as a novel, promising part of the combined antidepressant therapy. However, further studies on this subject are needed.