EFFECT OF THE AMPA RECEPTOR MODULATOR IDRA-21 ON LTP IN HIPPOCAMPAL SLICES

IDRA 21 oro-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 mu M) significantly increased the amp litude and halfwidth of field EPSPs. The drug did not affect monosynap tic IPSPs but enhanced disynaptically-induced feedforward IPSPs, presu mably by acting on AMPA receptors on interneurons. At concentrations t hat 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 result s support the hypothesis that drugs which enhance AMPA receptor-mediat ed currents facilitate LTP.