Modification of adenosine modulation of synaptic transmission in the hippocampus of aged rats

We compared the modulation of synaptic transmission by adenosine A 1 receptors in the hippocampus of aged (24 months) and young adult rats (6 weeks). The adenosine A 1 receptor agonist, N 6 ‐cyclopentyladenosine, was less potent ( P <0.05) to inhibit synaptic transmission in aged (EC 50 =53 n M ) than young adult (EC 50 =14 n M ) hippocampal slices, these effects being prevented by the A 1 receptor antagonist, 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX). In contrast with the lower effect of the A 1 receptor agonist, it was observed that blockade of A 1 receptors with DPCPX (50 n M ), or removal of endogenous extracellular adenosine with adenosine deaminase (2 u ml −1 ), caused a more pronounced disinhibition of synaptic transmission in aged rats. Also consistent with a more intense A 1 receptor‐mediated inhibitory tonus by endogenous adenosine in aged rats was the finding that to fully prevent the depression of synaptic transmission induced by 3 min hypoxia, a higher concentration of DPCPX was required in slices from aged (100 n M ) than from young (50 n M ) rats. It is concluded that in hippocampal slices of aged rats the efficiency of A 1 receptors to modulate synaptic transmission is reduced, but this may be compensated by an enhanced inhibitory tonus by endogenous adenosine.British Journal of Pharmacology (2000) 131 , 1629–1634; doi: 10.1038/sj.bjp.0703736