THE EFFECTS OF T-588, A NOVEL COGNITIVE ENHANCER, ON NORADRENALINE UPTAKE AND RELEASE IN RAT CEREBRAL CORTICAL SLICES

Previously, we reported that ophen-5-yl)-2-[2-(N,N-diethylamino)-ethox y]ethanol hydrochloride (T-588), a novel cognitive enhancer, stimulate d noradrenaline (NA) release from rat cerebral cortical slices. In thi s study, we investigated the effects of T-588 on NA uptake and release , compared to the effects of desipramine, a blocker of the NA carrier on the plasma membrane. Both T-588 and desipramine caused dose-depende nt inhibition of [H-3]NA uptake into the slices. Addition of 3 mM T-58 8 stimulated [H-3]NA release from the prelabeled slices even in the pr esence of 10 mu M desipramine, which inhibited NA uptake completely. T yramine, which accelerates NA carrier-mediated release, also stimulate d [H-3]NA release, and tyramine-stimulated release was inhibited by de sipramine. These findings indicated that T-588-stimulated NA release w as not mediated by 1) inhibition of reuptake or 2) reverse transport m ediated by NA carriers. Reserpine, which interacts with the intracellu lar vesicular transport system, increased [H-3]NA efflux from slices. High K+, not T-588-, stimulated [H-3]NA release was shifted upward by reserpine. These findings suggest that T-588 evokes NA release by a me chanism similar to that induced by reserpine. T-588 might act as a cog nitive enhancer via neurotransmitter release in the brain.