ZD7288-induced suppression of long-term potentiation was attenuated by exogenous NMDA at the Schaffer collateral-CA1 synapse in the rat in vivo.

Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels have been suggested to play an important role in the control of membrane excitability and rhythmic neuronal activity. Our previous study showed that the selective HCN channels blocker, ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride) can block the induction of long-term potentiation (LTP) in perforant path-CA3 region in rat hippocampus in vivo. In the present study, we investigated the effect of ZD7288 on synaptic transmission and high frequency stimulation (HFS)-induced LTP in the Schaffer collateral-CA1 synapse of rat hippocampus in vivo, and examined the possible relations between activation of N-methyl-d-aspartate (NMDA) type of glutamate receptor and HCN channels for induction of LTP. Application of ZD7288 modulated synaptic transmission and produced a dose-dependent inhibition of the induction of LTP, and the inhibitory action was partially reversed by the application of NMDA. In addition, ZD7288, when given 30 min after HFS, did not alter the maintenance of LTP. The results suggest that ZD7288 has the ability to prevent the induction of LTP at the Schaffer collateral-CA1 synapse of rat hippocampus, and that this inhibitory effect is attenuated by direct activation of the NMDA receptor.