THE 5-HT3 RECEPTOR ANTAGONIST, RS-56812, ENHANCES DELAYED MATCHING PERFORMANCE IN MONKEYS

SUBSTANTIAL evidence indicates that serotonin receptors are involved i n the regulation of acetylcholine release in CNS regions important to mnemonic processes, and may thus be exploited pharmacologically as tar gets for memory improvement. In the present study, the (R) and (S) iso mers of a potent serotonin (5-HT3) receptor ligand, RS-56812 were eval uated for potential tial memory effects in five macaques trained to pe rform a delayed matching-to-sample (DMTS) task. While both isomers enh anced certain aspects of task performance, the (R) isomer produced mor e systematic improvements. This differential sensitivity to the isomer s in regard to DMTS performance appears to parallel the higher 5-HT3 r eceptor affinity of the R enanantiomer. The results are consistent wit h a potential therapeutic role for RS-56812 in disorders involving cog nitive decline.