The present study investigated the effects of tacrine (an inhibitor of acetylcholinesterase) and zacopride (the antagonist of 5-HT3 receptors) on the performance of adult rats in a continuous operant delayed non-matching to position task assessing spatial working memory. 2. Adult rats had a decline in the percent correct responses at the longest delays (16 and 30 sec) in this task. Tacrine (1.0 mg/kg) or zacopride (0.0025, 0.05, 1.0 mg/kg) did not increase the percent correct responses at any time delays. The higher dose of tacrine reduced behavioural activity (e.g. the decreased number of trials completed and increased sample press latency) of rats during memory testing, and it slightly increased choice accuracy across all the delays. 3. The combination of zacopride (1.0 mg/kg) and tacrine (1.0 mg/kg) increased the percent correct responses at the shortest delays, but not at the longest delays. 4. These results indicate a non-mnemonic improvement in the accuracy performance of rats, and they suggest that the effects of acute, systemic administrations of zacopride (which is thought to increase the release of acetylcholine) or/and tacrine (which inhibits the breakdown of acetylcholine) do not improve spatial working/short-term memory in rats.
