MASKING OF FORSKOLIN-INDUCED LONG-TERM POTENTIATION BY ADENOSINE ACCUMULATION IN AREA CA1 OF THE RAT HIPPOCAMPUS

At hippocampal Schaffer collateral-CA1 synapses, activation of beta-ad renergic receptors and adenylyl cyclase increases transmitter release. However, this effect is transient, which is in contrast to that seen at mossy fiber-CA3 synapses, where activation of cyclic-AMP-dependent protein kinase results in long-lasting facilitation of transmitter rel ease, a phenomenon known as a presynaptic form of long-term potentiati on. The present study was aimed at investigating whether forskolin, an adenylyl cyclase activator, could produce long-term effects at the Sc haffer collateral-CA1 synapses using extracellular recording technique s. As has been reported previously, forskolin persistently increased t he amplitude of evoked population spikes without having a long-term ef fect on the field excitatory postsynaptic potentials. However, under t he conditions where adenosine A, receptors are inhibited, cyclic-AMP m etabolism is disrupted or the transport of cyclic-AMP is blocked; fors kolin induces long-term potentiation. Forskolin-induced potentiation i s associated with a decrease in paired-pulse facilitation and is block ed by the cyclic-AMP-dependent protein kinase inhibitor Rp-adenosine-3 ',5'-cyclic monophosphorothioate. Activation of Nw-methyl-D-aspartate receptors is not required for forskolin-induced long-term potentiation , because pretreatment of slices with the N-methyl-D-aspartate recepto r antagonist D-2-amino-5-phosphonovalerate did not prevent forskolin-i nduced potentiation. These results suggest that blockade of adenosine A(1) receptors unmasks forskolin-induced long-term potentiation, and a ctivation of cyclic-AMP-dependent protein kinase induces a form of lon g-term potentiation which is different from that induced by tetanic st imulation. (C) 1998 IBRO. Published by Elsevier Science Ltd.