Potential role of adenosine A2A receptors in the treatment of schizophrenia

Abstract

Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive deficits, and positive and negative symptoms. All antipsychotics currently used in clinical practice are dopamine D2 receptor antagonists. The idea that adenosine A2A receptor agonists might be of interest for the treatment of schizophrenia derived from studies showing the existence of antagonistic intramembrane interaction between A2A and D2 receptors. Based on results obtained in animal models, a putative antipsychotic-like profile of A2A agonists was put forward. However, A2A agonists were shown to have detrimental effects in animal models of learning and memory. Moreover, these compounds produce many peripheral side-effects which limits their use in clinical trials. On the other hand, The results concerning the influence of A2A receptor antagonists in animal models used in schizophrenia studies such as locomotor activity and prepulse inhibition are fairly controversial. Some cognitive enhancing properties of A2A receptor antagonists have also been found in rats. Recent results showing the existence of heteromeric A2A/D3 and A2A/mGlu5 receptor complexes seem to open up new perspectives on the search for novel therapies of schizophrenia.