Potential therapeutic interest of adenosine A2A receptors in psychiatric disorders.
The interest on targeting adenosine A(2A) receptors in the realm of psychiatric diseases first arose based on their tight physical and functional interaction with dopamine D(2) receptors. However, the role of central A(2A) receptors is now viewed as much broader than just controlling D(2) receptor function. Thus, there is currently a major interest in the ability of A(2A) receptors to control synaptic plasticity at glutamatergic synapses. This is due to a combined ability of A(2A) receptors to facilitate the release of glutamate and the activation of NMDA receptors. Therefore, A(2A) receptors are now conceived as a normalizing device promoting adequate adaptive responses in neuronal circuits, a role similar to that fulfilled, in essence, by dopamine. This makes A(2A) receptors particularly attractive targets to manage psychiatric disorders since adenosine may act as go-between glutamate and dopamine, two of the key players in mood processing. Furthermore, A(2A) receptors also control glia function and brain metabolic adaptation, two other emerging mechanisms to understand abnormal processing of mood, and A(2A) receptors are important players in controlling the demise of neurodegeneration, considered an amplificatory loop in psychiatric disorders. Current data only provide an indirect confirmation of this putative role of A(2A) receptors, based on the effects of caffeine (an antagonist of both A(1) and A(2A) receptors) in psychiatric disorders. However, the introduction of A(2A) receptors antagonists in clinics as anti-parkinsonian agents is hoped to bolster our knowledge on the role of A(2A) receptors in mood disorders in the near future.
Cunha
Rodrigo A
RA
Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Portugal. cunharod@gmail.com
Ferré
Sergi
S
Vaugeois
Jean-Marie
JM
Chen
Jiang-Fan
JF
D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000378:metabolism; D003863:Depression / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology
D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2