Adenosine A2A receptors and their role in drug addiction

The specific events between initial presumably manageable drug intake and the development of a drug-addicted state are not yet known. Drugs of abuse have varying mechanisms of action that create a complex pattern of behaviour related to drug consumption, drug-seeking, withdrawal and relapse. The neuromodulator adenosine has been shown to play a role in reward-related behaviour, both as an independent mediator and via interactions of adenosine receptors with other receptors. Adenosine levels are elevated upon exposure to drugs of abuse and adenosine A(2A) receptors are enriched in brain nuclei known for their involvement in the processing of drug-related reinforcement processing. A(2A) receptors are found in receptor clusters with dopamine and glutamate receptors. A(2A) receptors are thus ideally situated to influence the signalling of neurotransmitters relevant in the neuronal responses and plasticity that underlie the development of drug taking and drug-seeking behaviour. In this review, we present evidence for the role of adenosine and A(2A) receptors in drug addiction, thereby providing support for current efforts aimed at developing drug therapies to combat substance abuse that target adenosine signalling via A(2A) receptors.