Involvement of the adenosine A1 and A2A receptors in the antidepressant-like effect of zinc in the forced swimming test

It was previously shown that the acute administration of zinc chloride elicits an antidepressant-like effect in the mouse forced swimming test (FST). We have also shown that the activation of adenosine A₁ and A_2A receptors produces an antidepressant-like effect in FST. Thus, this study investigated the involvement of adenosine receptors in the antidepressant-like effect of zinc in the FST. The antidepressant-like effect of ZnCl₂ (30 mg/kg, i.p.) in the FST was prevented by the pretreatment of animals with caffeine (3 mg/kg, i.p., a non-selective adenosine receptor antagonist), DPCPX (2 mg/kg, i.p., a selective adenosine A₁ receptor antagonist) or ZM241385 (1 mg/kg, i.p., a selective adenosine A_2A receptor antagonist), administered at doses that per se produced no anti-immobility effect. Moreover, the treatment of mice with CHA (0.05 mg/kg, i.p., a selective adenosine A₁ receptor agonist), DPMA (0.1 mg/kg, i.p., a selective adenosine A_2A receptor agonist) or dipyridamole (0.1 µg/site, i.c.v., an adenosine transporter inhibitor) was able to potentiate the action of sub-effective doses of ZnCl₂. Taken together, the results suggest that the antidepressant-like effect of zinc in the mouse FST might involve a direct or indirect activation of adenosine A₁ and A_2A receptors.