Reversal of pentylenetetrazol-induced potentiation phenomenon by theta pulse stimulation in the CA1 region of rat hippocampal slices

The effect of theta pulse stimulation (TPS) on pentylenetetrazol (PTZ)-induced long-term potentiation of population spikes was studied in the CA1 region of rat hippocampal slices. The field excitatory postsynaptic potential (fEPSP) and population spikes (PS) were recorded from strata radiatum and pyramidale, respectively, following stimulation of Schaffer collaterals. A transient PTZ application produced a long-lasting enhancement of PS amplitude. A 3-min episode of TPS delivered at test-pulse intensity failed to reverse the PTZ potentiation. However, the same stimulation at a higher intensity produced complete reversal of the PTZ potentiation when delivered during the last minutes of PTZ application. Prior application of high-intensity TPS also decreased the amount of PTZ potentiation, whereas it had no long-lasting effect on baseline synaptic responses. High-intensity TPS induced reversal was blocked by adenosine A1 receptor antagonist and, furthermore, was reduced by protein phosphatase 1 inhibitor. The results suggest that mechanism of PTZ-induced LTP reversal involves activation of adenosine receptors and protein phosphatases.