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 tested for its ability to improve impaired recent memory of aged mice. All mice successfully acquired a learning set for accurate identification of the correct arm of a T-maze and could perform with nearly 100% accuracy after 1-min delays. However, performance of the aged mice approached chance levels after 2-h delays. When injected just before testing on a series of 2-h retention tests, RO 15-3505 (from 2.5-3505 (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 modulation of memory processes, and suggest that the memory-facilitating effects RO 15-3505 or similar benzodiazepine receptor ligands may be generalized to aged rodents with impaired memory function.