Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor

Catherine Ledent, Jean-Marie Vaugeois, Serge N. Schiffmann, Thierry Pedrazzini, Malika El Yacoubi, Jean-Jacques Vanderhaeghen, Jean Costentin, John K. Heath, Gilbert Vassart and Marc Parmentier ()
Additional contact information
Catherine Ledent: IRIBHN, Université Libre de Bruxelles, Campus Erasme
Jean-Marie Vaugeois: IFRMP, Unité de Neuropsychopharmacologie Expérimentale, CNRS UPRESA 6036, Faculté de Médecine et de Pharmacie, Avenue de l'Université
Serge N. Schiffmann: Laboratoire de Recherche sur les Neuropeptides, Université Libre de Bruxelles, Campus Erasme
Thierry Pedrazzini: Lausanne University Medical School
Malika El Yacoubi: IFRMP, Unité de Neuropsychopharmacologie Expérimentale, CNRS UPRESA 6036, Faculté de Médecine et de Pharmacie, Avenue de l'Université
Jean-Jacques Vanderhaeghen: Laboratoire de Recherche sur les Neuropeptides, Université Libre de Bruxelles, Campus Erasme
Jean Costentin: IFRMP, Unité de Neuropsychopharmacologie Expérimentale, CNRS UPRESA 6036, Faculté de Médecine et de Pharmacie, Avenue de l'Université
John K. Heath: CRC Growth Factors, University of Oxford
Gilbert Vassart: IRIBHN, Université Libre de Bruxelles, Campus Erasme
Marc Parmentier: IRIBHN, Université Libre de Bruxelles, Campus Erasme

Nature, 1997, vol. 388, issue 6643, 674-678

Abstract: Abstract Adenosine is released from metabolically active cells by facilitated diffusion, and is generated extracellularly by degradation of released ATP. It is a potent biological mediator that modulates the activity of numerous cell types, including various neuronal populations, platelets, neutrophils and mast cells, and smooth muscle cells in bronchi and vasculature. Most of these effects help to protect cells and tissues during stress conditions such as ischaemia. Adenosine mediates its effects through four receptor subtypes: the A1, A2a, A2b and A3 receptors1. The A2a receptor (A2aR)2,3 is abundant in basal ganglia, vasculature and platelets, and stimulates adenylyl cyclase. It is a major target of caffeine, the most widely used psychoactive drug4. Here we investigate the role of the A2a receptor by disrupting the gene in mice. We found that A2aR-knockout (A2aR−/−) mice were viable and bred normally. Their exploratory activity was reduced, whereas caffeine, which normally stimulates exploratory behaviour, became a depressant of exploratory activity. Knockout animals scored higher in anxiety tests, and male mice were much more aggressive towards intruders. The response of A2aR−/−mice to acute pain stimuli was slower. Blood pressure and heart rate were increased, as well as platelet aggregation. The specific A2a agonist CGS 21680 lost its biological activity in all systems tested.

Date: 1997
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DOI: 10.1038/41771

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