Linopirdine does not improve matching performance in the titrating matching-to-sample paradigm

Abstract

Linopirdine (DUP 996), a proposed cognitive enhancing agent, was studied in four squirrel monkeys ( Saimiri sciureus) and six White Carneau pigeons responding under a titrating matching-to-sample paradigm (TMTS). Briefly, under this titration schedule, each trial began with the presentation of a sample stimulus on the center key of a three-key pigeon or squirrel monkey chamber. Completion of a fixed-ratio on the center key resulted in the termination of the stimulus presentation and the initiation of a delay period. The length of the delay changed as a function of the subject's performance. During the first five trials of each session, the delay was fixed at 3 s in length. On the sixth and all subsequent trials, the length of the delay increased, did not change, or decreased such that accuracy was maintained at approximately 80%. Following the delay, two of the three response keys were transilluminated with different colored lights. A single response on the key transilluminated with the same stimulus as the sample stimulus resulted in the presentation of food. A response on the key transilluminated with the stimulus that did not match the sample stimulus resulted in a timeout. Linopridine was administered in the pigeon (0.001–5.6 mg/kg) and squirrel monkey (0.01–1.0 mg/kg) 15 min before testing. Matching performance was not affected as measured by changes in mean delay values or percent accuracy even at doses that decreased rate of responding. These results suggest that the enhancement in cognitive function previously reported after administration of linopiridine may be limited to specific situations.