ADENOSINE A(2) RECEPTOR MEDIATION OF PRE-SYNAPTIC AND POSTSYNAPTIC EXCITATORY EFFECTS OF ADENOSINE IN RAT HIPPOCAMPUS IN-VITRO

Excitatory effects of adenosine in the rat hippocampus were studied by intracellular recording from CAl pyramidal cells in vitro. Applicatio n of 100 mu M adenosine induced a rapid hyperpolarization and a decrea se in input resistance, and depressed the excitatory postsynaptic pote ntials (EPSPs) evoked by stimulation of Schaffer collaterals in all ne urons tested. In 55% of the neurons this was followed by an excitation . This excitation consisted of a slow depolarization lasting 9 +/- 4.7 min, an increase in input resistance and an increase in the amplitude of the evoked EPSPs. This excitation could also be observed when syna ptic transmission was prevented by 1 mu M tetrodotoxin (tetrodotoxin). In the presence of 5 mu M 8-(p-sulphophenyl)theophylline (8-SPT) aden osine (10 mu M) enhanced the amplitude of evoked EPSPs by 20% +/- 3.6 (n = 5) in all neurons tested. Chloroadenosine (chloroadenosine; a sta ble analog of adenosine; 20 mu M) induced a similar hyperpolarization associated with decrease in input resistance; this was followed by a s imilar excitation as seen with adenosine in 22 of the 27 neurons teste d. L-baclofen (20 mu M) induced a hyperpolarization associated with de crease in input resistance in all six neurons tested but an ensuing ex citation was not observed. CGS 21680 (30 nM), a selective adenosine A( 2) receptor agonist, induced a slow depolarization associated with an increase in input resistance and, in 11 of 36 neurons, enhanced the am plitude of evoked EPSPs. These excitatory effects of CGS 21680 were bl ocked by the selective adenosine A(2) receptor antagonist, 3,7-dimethy l-1-propargylxanthine (DMPX, 10 mu M). In the presence of 1 mu M tetro dotoxin 30 nM CGS 21680 still produced a slow depolarization and an in crease in input resistance. In addition, high doses of CGS 21680 (10 a nd 20 mu M) depressed the amplitude of EPSPs evoked by stimulation of Schaffer collateral afferents, yet there was little effect on the rest ing membrane potential or input resistance despite the fact that 20 mu M chloroadenosine caused a pronounced hyperpolarization associated wi th a decrease in input resistance in the same cell. These results indi cate that the excitatory effects of adenosine may be mediated via acti vation of adenosine A, receptors at both presynaptic and postsynaptic sites in the hippocampal CAl region. (C) 1998 Elsevier Science B.V.