AGGRESSIVENESS, HYPOALGESIA AND HIGH BLOOD-PRESSURE IN MICE LACKING THE ADENOSINE A(2A) RECEPTOR

Adenosine is released from metabolically active cells by facilitated d iffusion, 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, platelet s, neutrophils and mast cells, and smooth muscle cells in bronchi and vasculatue. Most of these effects help to protect cells and tissues du ring stress conditions such as ischaemia. Adenosine mediates its effec ts through four receptor subtypes: the A(1), A(2a), A(2b) and A(3) rec eptors(1). The A(2a) receptor (A(2a)R)(2,3) is abundant in basal gangl ia, vasculature and platelets, and stimulates adenylyl cyclase. It is a major target of caffeine, the most widely used psychoactive drug(4). Here we investigate the role of the A(2a) receptor by disrupting the gene in mice. Here found that A(2a)R-knockout (A(2a)R(-/-)) mice were viable and bred normally. Their exploratory activity was reduced, wher eas caffeine, which normally stimulates exploratory behaviour, became a depressant of exploratory activity. Knockout animals scored higher i n anxiety tests, and male mice were much more aggressive towards intru ders. The response of A(2a)R(-/-) mice to acute pain stimuli was slowe r. Blood pressure and heart rate were increased, as well as platelet a ggregation. The specific A(2a) agonist CGS 21680 lost its biological a ctivity in all systems tested.