Effects of nicotine and mecamylamine on cognition in rhesus monkeys

Rationale: Nicotine and other agonists of nicotinic cholinergic receptors (nAChR) have been shown to improve performance in specific memory domains in rodents and monkeys. Such beneficial effects are observed in preclinical models of age-related cognitive decline, stimulating interest in nAChR ligands as possible therapeutics. Prior work has typically focused on assays of spatial working memory in rodent studies and visual recognition memory in monkey studies. Objective: The current study was conducted to determine the role played by nAChRs in multiple types of memory in monkeys. Methods: Rhesus monkeys (n=6) were trained to perforin a battery of six behavioral tasks and then serially challenged with acute doses of nicotine (3.2-56 mug/kg, IM) and the nAChR antagonist mecamylamine (0.32-1.78 mg/kg.. IM). Results: Nicotine improved performance on tests designed to assay visual recognition memory, spatial working memory and visuo-spatial associative memory, while mecamylamine impaired visuo-spatial associative memory. Ballistic and fine motor performance was not significantly improved by nicotine but fine motor performance was impaired by mecamylamine. Conclusions: Although nicotine may improve performance in multiple domains, effects on visuo-spatial associative memory is the most specifically attributable to nAChR signaling.