Ischaemic damage in gerbil hippocampus is reduced following upregulation of adenosine (A1) receptors by caffeine treatment.

We have used the fact that long-term caffeine treatment upregulates the adenosine receptors, to examine the role of adenosine in ischaemia. Four-week oral treatment with caffeine (0.2% in drinking water) caused a significant (10-17%) increase in the binding of the adenosine A1-receptor ligand [3H]cyclohexyl-adenosine (CHA) to several brain regions, including the hippocampal CA1 area, in Mongolian gerbils. Animals subjected to such treatment exhibited significantly less neuronal damage in the CA1 region following 5 min bilateral carotid occlusion than did control animals (50% of the caffeine-treated animals showed no damage at all compared to 11% in the control group). Our findings provide further evidence for a protective role of endogenous adenosine during ischaemia.