Adenosinergic-Dopaminergic Signaling in Mood Disorders: A Mini-Review

Mood disorders are one of the biggest health problems, affecting the patients' emotional state, who experience depression or extreme euphoria or both of these. This review will focus on the participation of adenosinergic signaling in major depressive disorder and bipolar disorder (BPD) as well as in schizophrenia and schizoaffective disorder. Adenosine receptor activation may induce antidepressive actions in animal models, either by enhancing the A(1)receptor or decreasing the A(2A)receptor activity. On the contrary, A(1)receptor activation can lead to manic-like behaviors in BPD models. Strong evidence points to adenosine modulation of the dopaminergic system, which has an important role in the pathophysiology of mood disorders. Most notable are the adenosine-dopamine receptor heteromers. Two of them, A(2A)-D(2)and A(1)-D(1)receptor dimers, are well characterized, but A(2A)-D-3, A(2A)-D-4, and A(2A)-D-2-D(3)receptors heteromers have also been suggested. A(2A)-D(2)heteromers are highly expressed in corticostriatal pathways, which, in turn, are linked to the pathophysiology of mood disorders. Thus, further research on the role of adenosine-dopamine receptor heteromers in mood control may lead to a better understanding of mood disorders' pathophysiology and novel therapeutic tools.