Effect of A(2A) adenosine receptor stimulation and antagonism on synaptic depression induced by in vitro ischaemia in rat hippocampal slices

1 In the present study we investigated the role of A(2A) adenosine receptor s in hippocampal synaptic transmission under in vitro ischaemia-like condit ions. 2 The effects of adenosine, of the selective A(2A) receptor agonist, CGS 21 680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosine), and of selective A(2A) receptor antagonists, ZM 241385 (4-(2-[7-amino-2-(2 -furyl)-{1,2,4}-triazolo{2,3-a}{1,3,5}triazin-5-ylamino]ethyl)phenol) and S CH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-tria zolo[1,5-c]pyrimidine), have been evaluated on the depression of field e.p. s.ps induced by an in vitro ischaemic episode. 3 The application of 2 min of in vitro ischaemia brought about a rapid and reversible depression of field e.p.s.ps, which was completely prevented in the presence of the A(1) receptor antagonist DPCPX (1,3-dipropyl-8-cyclopen tylxanthine) (100 nM). On the other hand both A(2A) receptor antagonists, Z M 241385 and SCH 58261, by themselves did not modify the field e.p.s.ps dep ression induced by in vitro ischaemia. 4 A prolonged application of either adenosine (100 mu M) or CGS 21680 (30, 100 nM) before the in vitro ischaemic episode, significantly reduced the sy naptic depression. These effects were antagonized in the presence of ZM 241 355 (100 nM). 5 SCH 58261 (1 and 50 nM did not antagonize the effect of 30 nM CGS 21680 o n the ischaemia-induced depression. 6 These results indicate that in the CA1 area of the hippocampus the stimul ation of A,, adenosine receptors attenuates the A(1)-mediated depression of synaptic transmission induced by in vitro ischaemia.