Evaluation of antidepressant-like and anxiolytic-like activity of purinedione-derivatives with affinity for adenosine A2A receptors in mice

Background: It has recently been suggested that the adenosine A(2A) receptor plays a role in several animal models of depression. Additionally, A(2A) antagonists have reversed behavioral deficits and exhibited a profile similar to classical antidepressants. Methods: In the present study, imidazo- and pyrimido[2,1-f]purinedione derivatives (MD 66, MD 167, MD 206) with affinity to A(2A) receptors but poor A1 affinity were evaluated for their antidepressant- and anxiolytic-like activity. The activity of these derivatives was tested using a tail suspension and forced swim test, two widely-used behavioral paradigms for the evaluation of antidepressant-like activity. In turn, the anxiolytic activity was evaluated using the four-plate test. Results: The results showed the antidepressant-like activity of pyrimido- and imidazopurinedione derivatives (i.e. MD 66, MD 167 and MD 206) in acute and chronic behavioral tests in mice. MD 66 revealed an anxiolytic-like effect, while MD 167 increased anxiety behaviors. MD 206 had no effect on anxiety. Furthermore, none of the tested compounds increased locomotor activity. Conclusion: Available data support the proposition that the examined compounds with adenosine A(2A) receptor affinity may be an interesting target for the development of antidepressant and/or anxiolytic agents. (C) 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.