Nootropic effect of nicotine on carbon monoxide (CO)-induced delayed amnesia in mice

The effects of nicotine on carbon monoxide (CO)-induced amnesia in mice were investigated using a step-down type passive avoidance task. Mice were exposed to CO 3 times at 1-h intervals, 7 days before the first training and retention test and 24 h after the first training session. Memory deficiency occurred in mice when training commenced more than 3 days after CO exposure (delayed amnesia): the median step-down latency in the retention test of the CO-exposed group was significantly shorter than that of the control group. Administration of (-)-nicotine (15.6 and 31.3 nmol/kg, IP) 15 min before the first training session prolonged the step-down latency in the CO-exposed group, but (+)-nicotine did not. To determine whether this effect of (-)-nicotine was mediated via nicotinic cholinergic receptors, we attempted to block its action using a nicotinic acetylcholine receptor antagonist (mecamylamine). Mecamylamine (1.25 mumol/kg) blocked the effect of (-)-nicotine (31.3 nmol/kg) on delayed amnesia. Administration of (-)-nicotine (15.6-62.5 nmol/kg) immediately after the first training session failed to ameliorate learning ability in the CO-exposed group. These results suggest that (-)-nicotine potentiates the nicotinic cholinergic neuronal system and may potentiate acquisition of memory.