The adenosine A2A receptor knockout mouse: a model for anxiety?

The main behavioural features of the adenosine A(2A) receptor knockout mouse include anxiety, aggressiveness in males and a paradoxical response to caffeine. These behavioural characteristics caused by the lack of adenosine A(2A) receptor function in mice correspond to the effects of functional antagonism of adenosine A(2A) receptors in humans and rodents. Increased anxiety in patients with panic disorder and increased psychotic symptomatology in patients with schizophrenia have been observed after caffeine administration. Several hypotheses have been developed suggesting a reduced adenosine A(2A) receptor-mediated transmission as a contributing factor in the pathogenesis of these disorders. Recent genetic studies, in particular of panic disorder, suggest an involvement of adenosine A(2A) receptor gene variation. If future studies prove a pathogenetic role for a genetically determined loss of A(2A) receptor function in psychiatric disorders, the A(2A) receptor knockout mouse will be a valuable model to develop novel pharmacological therapies for these disorders.