Dose-specific improvements in memory-related task performance by rats and aged monkeys administered the nicotinic-cholinergic antagonist mecamylamine

The centrally acting nicotinic-cholinergic antagonist mecamylamine (mec) is well documented to produce amnestic effects in animals and humans. However , in certain circumstances the compound has enhanced performance of some me mory-related tasks in animals and further investigation of this paradoxical effect is warranted. The present study was designed to determine under wha t conditions mec would enhance memory-task performance in rats and aged non human primates. Mec (various doses) or saline was administered IP to rats t ested in the Morris Water Maze (MWM), to rats trained to perform a delayed stimulus discrimination task (DSDT), and IM to aged rhesus monkeys (average age 24.6 years) trained to perform a delayed matching to sample task (DMTS ). In rats, mec 1.0 mg/kg improved location of the hidden platform on day 1 of the MWM, but inhibited learning in subsequent trials, while several mu g/kg doses improved DSDT accuracy. Further, some mu g/kg doses of mec also improved accuracy in aged monkeys in DMTS at both 10 min and 24 h after adm inistration. Mec had no effect on swim speeds in the MWM, response latencie s in the DSDT, or on choice or response latencies in the DMTS task. Collectively, the results indicate that some doses of mec can mimic certain memory-enhancing effects produced by nicotinic-acetylcholine receptor agon ists. It is not clear whether mec is acting as a partial agonist in this re gard, or whether low-level nicotinic antagonism produces a cellular respons e that is in some way analogous to nicotine-induced receptor desensitizatio n. (C) 1999 Wiley-Liss, Inc.