Serotonin 5-HT_1A receptors and their interactions with adenosine A_2A receptors in Parkinson's disease and dyskinesia

The dopamine neuronal loss that characterizes Parkinson's Disease (PD) is associated to changes in neurotransmitters, such as serotonin and adenosine, which contribute to the symptomatology of PD and to the onset of dyskinetic movements associated to levodopa treatment. The present review describes the role played by serotonin 5-HT_1A receptors and the adenosine A_2A receptors on dyskinetic movements induced by chronic levodopa in PD. The focus is on preclinical and clinical results showing the interaction between serotonin 5-HT_1A receptors and other receptors such as 5-HT_1B receptors and adenosine A_2A receptors. 5-HT_1A/1B receptor agonists and A_2A receptor antagonists, administered in combination, contrast dyskinetic movements induced by chronic levodopa without impairing motor behaviour, suggesting that this drug combination might be a useful therapeutic approach for counteracting the PD motor deficits and dyskinesia associated with chronic levodopa treatment. This article is part of the Special Issue on "The receptor-receptor interaction as a new target for therapy".