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

1 We compared the modulation of synaptic transmission by adenosine Al receptors in the hippocampus of aged (24 months) and young adult rats (6 weeks). 2 The adenosine A(1) receptor agonist, N(6)-cyclopentyladenosine, was less potent (P < 0.05) to inhibit synaptic transmission in aged (EC(50) = 53 nM) than young adult (EC(50) = 14 nM) hippocampal slices, these effects being prevented by the A(l) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). 3 In contrast with the lower effect of the A(1) receptor agonist, it was observed that blockade of A(1) receptors with DPCPX (50 nM), 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 nM) than from young (50 nM) rats. 4 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.