1-BCP, A MEMORY-ENHANCING AGENT, SELECTIVELY POTENTIATES AMPA-INDUCED[H-3] NOREPINEPHRINE RELEASE IN RAT HIPPOCAMPAL SLICES

It is now clear that the AMPA subtype of ionotropic glutamate receptor s (iGluRs) undergoes a rapid desensitization in response to activation by AMPA receptor agonists. This desensitization is inhibited by compo unds such as aniracetam and cyclothiazide, which act at a distinct sit e on the AMPA receptor complex. In particular, cyclothiazide greatly p otentiates AMPA receptor-mediated depolarizing responses in the hippoc ampus. We have recently shown cyclothiazide also increases AMPA-induce d release of [H-3]norepinephrine ([H-3]NE). More, recently, a benzamid e compound, 1-(1,3-benzodioxol-5-ylcarbonyl)-piperidine (1-BCP), has b een reported to enhance AMPA-induced currents and to facilitate memory retention in rats in a number of memory tasks. In this study, the eff ects of 1-BCP on excitatory amino acid agonist-induced [H-3]NE release in rat hippocampal slices were determined. We report that 1-BCP, like cyclothiazide, selectively potentiates AMPA-induced [H-3]NE release. However, cyclothiazide was more potent and efficacious than 1-BCP. Nev ertheless, these data suggest a role for AMPA receptor-mediated enhanc ement of norepinephrine release as a mechanism of action for nootropic compounds such as 1-BCP.