A ROLE FOR ADENOSINE A(2) RECEPTORS IN THE INDUCTION OF LONG-TERM POTENTIATION IN THE CA1 REGION OF RAT HIPPOCAMPUS

Although reductions in neurotransmission have been reported in respons e to agonist-mediated adenosine A(1) receptor activation, the implicat ions of A(2) receptor activation on synaptic transmission have not bee n well explored. We examined the role adenosine A(2) receptors play in the efficacy of neurotransmission between the Schaffer collateral-CA1 pathway in the rat transverse hippocampal slice. A(2) receptor blocka de in the presence of complete A(1) receptor inhibition led to a rever sible reduction of the field excitatory post-synaptic potential (EPSP) slope in response to low-frequency test pulses (0.033 Hz) indicating that A(2) receptors can enhance synaptic transmission. A(2) receptor b lockade by the A(2) antagonist, DMPX (3,7-dimethyl-1-propargylxanthine ) prevented the induction of tetanus-induced long-term potentiation (L TP) of the EPSP. In contrast, no such effect on LTP induction was obse rved during A(1) receptor blockade. We also examined the effects of DM PX on the induction of LTP during continued A(1) receptor blockade wit h CPT. Under this condition, LTP was significantly reduced when compar ed to LTP induced in the presence of CPT alone. A similar result was f ound using the highly polar A(2) antagonist 8-SPT (8-(p-sulfophenyl)th eophylline) suggesting that the effects of DMPX on LTP were not due to a direct action on an intracellular intermediate. DMPX had no effect on LTP expression if applied 45 min following the tetanus indicating t hat A(2) receptors play no significant role in the maintenance phase o f LTP. Selective A(2a) receptor activation did not alter the field EPS P. Similarly, selective blockade of the A(2) receptor did not interfer e with tetanus-induced LTP. Increases in neuronal firing rates can res ult in elevations in the concentration of extracellular adenosine. Tog ether, these results suggest that the A(2) receptors may play an impor tant role in the induction although not the maintenance of hippocampal LTP and that the effect is likely to be mediated by the A(2b) recepto r.