Nicotine enhances delayed matching-to-sample performance by primates.

The non-human primate provides an excellent model for studies of learning and memory, and one particular test, the delayed matching-to-sample task, is performed in a similar manner by both humans and non-human primates. Five young adult macaques were employed in this study, displaying variable capacities for retention in the task. Baseline performance was very consistent and three levels of performance difficulties (95-100%, 80-85% and 65-75% correct choices) were employed by including several delay intervals (0-60 sec) in each session. A reproducible enhancement in performance by nicotine in macaques performing a delayed matching-to-sample task was demonstrated. Nicotine enhanced performance with an average increase of 10% at the longest retention delay interval. This beneficial effect of nicotine was abolished in animals pretreated with a low dose (0.5 mg/kg) of mecamylamine to block central nicotinic receptors. Selective blockade of peripheral nicotinic receptors with hexamethonium was without effect on the nicotine response. A high dose (2 mg/kg) of mecamylamine itself induced a marked inhibition of performance, while an equivalent dose of hexamethonium was without effect. These experiments point to the possibility that central nicotinic receptors may be exploited pharmacologically to enhance memory performance. In this respect it is interesting that nicotine was most effective at enhancing performance when recall was more difficult, that is, on the longer retention interval delays. This could signify that nicotine might be particularly effective in the most impaired individuals. Lastly, it is encouraging that the mecamylamine induced decrease in cognitive performance might provide a new model of memory impairment from which to study the pathogenesis and develop new pharmacological strategies for the dementias.