THE BENZODIAZEPINE RECEPTOR INVERSE AGONIST RO-15-3505 REVERSES RECENT MEMORY DEFICITS IN AGED MICE

The benzodiazepine receptor partial inverse agonist RO 15-3505 was tes ted for its ability to improve impaired recent memory of aged mice. Al l mice successfully acquired a learning set for accurate identificatio n of the correct arm of a T-maze and could perform with nearly 100% ac curacy after 1-min delays. However, performance of the aged mice appro ached chance levels after 2-h delays. When injected just before testin g on a series of 2-h retention tests, RO 15-3505 (from 2.5-10.0 mg/kg) resulted in a marked improvement of response accuracy. These results confirm the role of benzodiazepine receptor mechanisms in the modulati on of memory processes, and suggest that the memory-facilitating effec ts RO 15-3505 or similar benzodiazepine receptor ligands may be genera lized to aged rodents with impaired memory function.