New Modes of GPCR Signalling

ZD7288 Inhibits the Induction Of LTP in an NMDA Independent
Manner at Hippocampal Schaffer Collateral-CA1 Synapses
Wei He, Zhenyong Cheng, Shibin Li, Xulin Xu, Qing Lu, Lianjun Guo*
Department of Pharmacology, Tongji Medical College of Huazhong University of
Science and Technology, Wuhan, 430030, China
Aim: To investigate the effect of ZD7288 on synaptic transmission and high frequency
stimulation (HFS)-induced long-term potentiation(LTP) in the Schaffer collateral-CA1
synapse of mouse hippocampal slices, and identify whether the effect of ZD7288 on the
induction of LTP can be explained by inhibition of N-methyl-D-aspartate (NMDA) type
of glutamate receptors. Methods: Extracellular field excitatory postsynaptic
potentials(fEPSPs) recordings were used to examine the effect of ZD7288 on basal
synaptic transmission and HFS-induced LTP in the Schaffer collateral-CA1 synapse of
mouse hippocampal slices, and measured the evoked depolarisations that by direct
agonist NMDA receptors. Result: Bath application of 10 µM ZD7288 had no effect on
basal synaptic transmission but inhibited the induction of HFS-induced LTP. In addition,
10 µM ZD7288 had no effect on the responses to exogenous NMDA. Conclusion: The
results suggested that ZD7288 has the ability to prevent the induction of LTP at the
Schaffer collateral-CA1 synapse of mouse hippocampus in vitro, and this inhibitory
effect is an NMDA receptor independent manner.
Key Words: ZD7288; synaptic transmission; long-term potentiation; NMDA
Acknowledgments: This work was supported by grants from the National Natural
Science Foundation of China (NSFC, No. 30772559) to Lianjun Guo
First author : Wei He Tel: +86 27 83691762,E-mail: hewei8286291@yahoo.com.cn
* Correspondence author :Tel: +86 27 83691763, E-mail: gljyl@yahoo.com.cn