Effect of the AMPA receptor modulator IDRA 21 on LTP in hippocampal slices

IDRA 21 (7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide) has been reported to modulate AMPA receptor kinetics and to improve memory in certain animal models. In the present study, its effects on synaptic transmission and long-term potentiation (LTP) were tested in hippocampal slices. IDRA 21 (500 microM) significantly increased the amplitude and halfwidth of field EPSPs. The drug did not affect monosynaptic IPSPs but enhanced disynaptically-induced feedforward IPSPs, presumably by acting on AMPA receptors on interneurons. At concentrations that facilitated synaptic transmission, IDRA 21 promoted the induction of LTP; i.e. full potentiation was obtained with stimulation paradigms that were only partially effective in the absence of drug. The results support the hypothesis that drugs which enhance AMPA receptor-mediated currents facilitate LTP.