IMPROVEMENT IN ACCURACY OF DELAYED RECALL IN AGED AND NON-AGED, MATURE MONKEYS AFTER INTRAMUSCULAR OR TRANSDERMAL ADMINISTRATION OF THE CNSNICOTINIC RECEPTOR AGONIST ABT-418

ABT-418 was evaluated for its ability to enhance accuracy on a delayed matching-to-sample (DMTS) task by aged monkeys following intramuscula r administration, and in non-aged mature monkeys following transdermal application. Aged monkeys were impaired in their performance of the D MTS task such that the longest delay intervals performed at above-chan ce levels extended only to 20 s. In contrast, for non-aged, mature ani mals, delay intervals extended to 140 s. In aged monkeys, the response to ABT-418 was highly individualized with animals responding to one o r more doses in the range of 2-259 nmol/kg. A systematic dose-dependen t enhancement of DMTS accuracy was not observed. When the individualiz ed ''best dose'' was administered on a separate occasion, overall DMTS accuracy was increased by 12.6%. By 24 h after administration, accura cy was at control levels, In young monkeys, a significant dose-depende nt enhancement of DMTS performance (an overall increase of 11.25% abov e baseline accuracy) was observed 5 h after application of a transderm al patch designed to maintain steady-state plasma levels of ABT-418 of 40-60 ng/ml over a 24-h period. Again there was some individual respo nsiveness to one of the three doses. When data included only the indiv idualized best doses of ABT-418 for each animal, a similar enhancement of accuracy was observed for both the 5-h and 24-h test intervals. In neither the aged nor the young cohorts was enhancement of performance associated with altered response latencies or with any overt side eff ects of ABT-418. Thus, these data are consistent with the ability of A BT-418 to improve DMTS performance in both young and aged monkeys. In aged monkeys, this response was observed only after administration of individualized optimal doses for different monkeys. In young monkeys, a more systematic enhancement of DMTS accuracy was observed. Further, transdermal delivery of ABT-418 in non-aged monkeys demonstrated prolo nged performance enhancement compared with IM injection to at least 24 h after patch administration.