GPCR oligomerization as a target for antidepressants: Focus on GPR39

At present most of the evidence for the relevance of oligomerization for the pharmacology of depression comes from in vitro studies which identified oligomers, and from neuropsychopharmacological studies of receptors which participate in oligomerization. For example, behavioural and biochemical studies in knockout animals suggest that GPR39 may mediate the antidepressant action of monoaminergic antidepressants. We have recently found long-lasting antidepressant-like effects of GPR39 agonist, thus suggesting GPR39 as a target for the development of novel antidepressant drugs. In vitro studies have shown that GPR39 oligomerizes with other GPCRs. Oligomerization of GPR39 should thus be considered in relation to the development of new antidepressants targeting this receptor as well as antidepressants targeting other receptors that may form complexes with GPR39. Here, we summarize recent data suggestive of the importance of oligomerization for the pharmacology of depression and discuss approaches for validation of this phenomenon.