Effects of adenosine A_2A receptors on cognitive function in health and disease

Adenosine A_2A receptors have been studied extensively in the context of motor function and movement disorders such as Parkinson's disease. In addition to these roles, A_2A receptors have also been increasingly implicated in cognitive function and cognitive impairments in diverse conditions, including Alzheimer's disease, schizophrenia, acute brain injury, and stress. We review the roles of A_2A receptors in cognitive processes in health and disease, focusing primarily on the effects of reducing or enhancing A_2A expression levels or activities in animal models. Studies reveal that A_2A receptors in neurons and astrocytes modulate multiple aspects of cognitive function, including memory and motivation. Converging evidence also indicates that A_2A receptor levels and activities are aberrantly increased in aging, acute brain injury, and chronic disorders, and these increases contribute to neurocognitive impairments. Therapeutically targeting A_2A receptors with selective modulators may alleviate cognitive deficits in diverse neurological and neuropsychiatric conditions. Further research on the exact neural mechanisms of these effects as well as the efficacy of selective A_2A modulators on cognitive alterations in humans are important areas for future investigation.