Adenosine in the neurobiology of schizophrenia: potential adenosine receptor-based pharmacotherapy

The pharmacological treatment of schizophrenia is currently based on restoring striatal dopamine and prefrontal cortex glutamate neurotransmission. However, these therapies are usually insufficient to completely manage all disease symptoms (i.e., negative and cognitive symptoms). Thus, the study of alternative and/or complementary neurotransmitter systems, which might impinge onto the etiology of schizophrenia, constitutes a big challenge for modern neuropsychiatry. Adenosine is a well known neuromodulator in the central nervous system (CNS) with beneficial properties for a number of brain disorders. The physiological effects of this nucleoside are mediated by G protein-coupled adenosine receptors, which have clearly evolved as drug targets for the pharmacotherapy of certain CNS diseases (e.g., Parkinson disease). Interestingly, it has been demonstrated that adenosine is able to modulate not only the dopaminergic but also glutamatergic system, thus representing a promising candidate to restore the schizophrenia-associated dopamine-glutamate imbalance that may underlie the origins of the disease. Accordingly, the development of drugs targeting adenosine receptors will constitute a worthwhile challenge for current neuropharmacology, because these compounds will definitively enrich the pharmacological arsenal and the pharmacotherapeutic opportunities surrounding schizophrenia. Keywords Adenosine Adenosine receptors Schizophrenia