Cholinergic channel activator, ABT-418, enhances delayed response accuracy in rats

The purpose of this study was to evaluate ABT-418, a recently developed isoxasole bioisostere of nicotine and cholinergic channel activator (ChCA), in rats trained to perform a delayed-response task, the Delayed Stimulus Discrimination Task (DSDT). In dose-effect studies, ABT-418 improved DSDT performance, while mecamylamine decreased accuracy of the task. The improvements afforded by optimal doses of ABT-418 were further substantiated by repeated administration on a separate occasion. Surprisingly, mecamylamine (1.0 mg/kg), when combined with optimal doses of ABT-418, failed to prevent improvements in accuracy of the task, as it had in a previous study with nicotine. The basis for this effect is unclear but may be related to the purported subtype selectivity of ABT-418. None of the drug-induced changes in DSDT accuracy was modality specific (i.e., whether the stimulus was the presented light or tone), and none of the drug manipulations produced significant changes in response latencies. Overall, the data confirm findings of previous rodent and nonhuman primate studies, which indicate that the nicotinic ligand has the potential to improve memory.