Modulation of fast excitatory synaptic transmission by cyclothiazide and GYKI 52466 in the rat hippocampus

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Abstract

The effects of cyclothiazide, a drug which potentiates AMPA receptor-mediated responses and GYKI 52466, a non-competitive AMPA receptor antagonist, were studied on fast glutamatergic transmission in rat hippocampal slices. Cyclothiazide prolonged the decay of AMPA receptor-mediated EPSCs (AMPA-EPSCs) in a concentration-dependent manner. GYKI 52466 reduced the peak amplitude of AMPA-EPSCs and blocked the induction of LTP. When GYKI 52466 was applied in the presence of cyclothiazide it still reduced the peak amplitude of AMPA-EPSCs but was not able to reverse the cyclothiazide induced prolongation of AMPA-EPSC duration. These data suggest that GYKI 52466 and cyclothiazide probably mediate their effects on the AMPA receptor via different binding sites.

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    This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (Graduiertenkolleg, SFB 353) and through a Helmholtz-stipend to W.M. from the Bundesministerium für Forschung und Technologie.

    We thank G. L. Collingridge for critically reading the manuscript and K. Clark for advicing patiently on patch clamp recording in slices.

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